Author Report for: Johnson JNo contact information in database for Johnson J
Freyria NJ, Kuo A, Chovatia M, Johnson J, Lipzen A, Barry KW, Grigoriev IV, Lovejoy C Ref: Commun Biol, 5:500, 2022 : PubMed ESTHER: Freyria_2022_Commun.Biol_5_500 PubMedSearch: Freyria 2022 Commun.Biol 5 500 PubMedID: 35614207 Abstract Little is known at the transcriptional level about microbial eukaryotic adaptations to short-term salinity change. Arctic microalgae are exposed to low salinity due to sea-ice melt and higher salinity with brine channel formation during freeze-up. Here, we investigate the transcriptional response of an ice-associated microalgae over salinities from 45 to 8. Our results show a bracketed response of differential gene expression when the cultures were exposed to progressively decreasing salinity. Key genes associated with salinity changes were involved in specific metabolic pathways, transcription factors and regulators, protein kinases, carbohydrate active enzymes, and inorganic ion transporters. The pelagophyte seemed to use a strategy involving overexpression of Na(+)-H(+) antiporters and Na(+) -Pi symporters as salinity decreases, but the K(+) channel complex at higher salinities. Specific adaptation to cold saline arctic conditions was seen with differential expression of several antifreeze proteins, an ice-binding protein and an acyl-esterase involved in cold adaptation. Title: Complications After Dental Sedation: A Myotonic Mystery Case Report Karamlou M, Asaria I, Barron J, Boutros P, Fisher V, Grandinetti R, Johnson J, Richard E, Susko D and Hall D <7 more author(s)> Karamlou M, Asaria I, Barron J, Boutros P, Fisher V, Grandinetti R, Johnson J, Richard E, Susko D, Urrutia C, Woolsey B, Baumann R, Cottle J, Sweaney R, Wenzel M, Nusstein J, Hall D (- 7) Ref: Anesth Prog, 69:26, 2022 : PubMed ESTHER: Karamlou_2022_Anesth.Prog_69_26 PubMedSearch: Karamlou 2022 Anesth.Prog 69 26 PubMedID: 36534775 Abstract Myotonic dystrophy (dystrophia myotonica; DM) is an uncommon progressive hereditary muscle disorder that can present with variable severity at birth, in early childhood, or most commonly as an adult. Patients with DM, especially type 1 (DM1), are extremely sensitive to the respiratory depressant effects of sedative-hypnotics, anxiolytics, and opioid agonists. This case report describes a 37-year-old male patient with previously undiagnosed DM1 who received dental care under minimal sedation using intravenous midazolam. During the case, the patient experienced 2 brief episodes of hypoxemia, the second of which required emergency intubation after propofol and succinylcholine and resulted in extended hospital admission. A lipid emulsion (Liposyn II 20%) infusion was given approximately 2 hours after the last local anesthetic injection due to slight ST elevation and suspicion of local anesthetic toxicity (LAST). Months after treatment, the patient suffered a fall resulting in a fatal traumatic brain injury. Complications noted in this case report were primarily attributed to the unknown diagnosis of DM1, although additional precipitating factors were likely present. This report also provides a basic review of the literature and clinical guidelines for managing myotonic dystrophy patients for dental care with local anesthesia, sedation, or general anesthesia. Title: Amyloid Peptide Scaffolds Coordinate with Alzheimer's Disease Drugs Jonnalagadda SVR, Gerace AJ, Thai K, Johnson J, Tsimenidis K, Jakubowski JM, Shen C, Henderson KJ, Tamamis P, Gkikas M Ref: J Phys Chem B, 124:487, 2020 : PubMed ESTHER: Jonnalagadda_2020_J.Phys.Chem.B_124_487 PubMedSearch: Jonnalagadda 2020 J.Phys.Chem.B 124 487 PubMedID: 31881810 Abstract Functional amyloid materials can combine the self-assembly of peptide scaffolds into amyloid fibrils with binding capacities for ions or compounds of pharmaceutical interest, endowed by mutable non-beta-sheet-forming residues at the termini. Herein, we report the first to our knowledge amyloid materials, encompassing a GAIIG amyloidogenic core, which bind to Alzheimer's disease (AD) drugs, by mimicking the mechanism by which the same AD drugs bind to enzymes according to experimentally resolved structures, including the target enzyme acetylcholinesterase (AChE). The computationally designed amyloid scaffolds are experimentally shown to coordinate with AD drugs, using two techniques, both in dilute solutions and at higher peptide concentrations, with a higher binding capacity for donepezil and tacrine compared to that for memantine and galantamine. The binding for some of the AD drugs is strong and stable even after extensive subsequent aqueous washings, denoting high capturing efficiency by the designed biomaterials, even after incubation under physiological conditions. Our findings constitute starting points to design novel drug delivery carriers binding to one or combinations of AD drugs (e.g., NMDA and cholinesterase inhibitors). Title: Comprehensive genomic and transcriptomic analysis of polycyclic aromatic hydrocarbon degradation by a mycoremediation fungus, Dentipellis sp. KUC8613 Park H, Min B, Jang Y, Kim J, Lipzen A, Sharma A, Andreopoulos B, Johnson J, Riley R and Choi IG <5 more author(s)> Park H, Min B, Jang Y, Kim J, Lipzen A, Sharma A, Andreopoulos B, Johnson J, Riley R, Spatafora JW, Henrissat B, Kim KH, Grigoriev IV, Kim JJ, Choi IG (- 5) Ref: Applied Microbiology & Biotechnology, 103:8145, 2019 : PubMed ESTHER: Park_2019_Appl.Microbiol.Biotechnol_103_8145 PubMedSearch: Park 2019 Appl.Microbiol.Biotechnol 103 8145 PubMedID: 31482283 Gene_locus related to this paper: 9agam-a0a5b1qnb8, 9agam-a0a5b1qwq3, 9agam-a0a5b1qh04, 9agam-a0a5b1qyk1, 9agam-a0a5b1qmi3, 9agam-a0a5b1qi91, 9agam-a0a5b1qhi2 Abstract The environmental accumulation of polycyclic aromatic hydrocarbons (PAHs) is of great concern due to potential carcinogenic and mutagenic risks, as well as their resistance to remediation. While many fungi have been reported to break down PAHs in environments, the details of gene-based metabolic pathways are not yet comprehensively understood. Specifically, the genome-scale transcriptional responses of fungal PAH degradation have rarely been reported. In this study, we report the genomic and transcriptomic basis of PAH bioremediation by a potent fungal degrader, Dentipellis sp. KUC8613. The genome size of this fungus was 36.71 Mbp long encoding 14,320 putative protein-coding genes. The strain efficiently removed more than 90% of 100 mg/l concentration of PAHs within 10 days. The genomic and transcriptomic analysis of this white rot fungus highlights that the strain primarily utilized non-ligninolytic enzymes to remove various PAHs, rather than typical ligninolytic enzymes known for playing important roles in PAH degradation. PAH removal by non-ligninolytic enzymes was initiated by both different PAH-specific and common upregulation of P450s, followed by downstream PAH-transforming enzymes such as epoxide hydrolases, dehydrogenases, FAD-dependent monooxygenases, dioxygenases, and glycosyl- or glutathione transferases. Among the various PAHs, phenanthrene induced a more dynamic transcriptomic response possibly due to its greater cytotoxicity, leading to highly upregulated genes involved in the translocation of PAHs, a defense system against reactive oxygen species, and ATP synthesis. Our genomic and transcriptomic data provide a foundation of understanding regarding the mycoremediation of PAHs and the application of this strain for polluted environments. Title: Comparative genomics provides insights into the lifestyle and reveals functional heterogeneity of dark septate endophytic fungi Knapp DG, Nemeth JB, Barry K, Hainaut M, Henrissat B, Johnson J, Kuo A, Lim JHP, Lipzen A and Kovacs GM <6 more author(s)> Knapp DG, Nemeth JB, Barry K, Hainaut M, Henrissat B, Johnson J, Kuo A, Lim JHP, Lipzen A, Nolan M, Ohm RA, Tamas L, Grigoriev IV, Spatafora JW, Nagy LG, Kovacs GM (- 6) Ref: Sci Rep, 8:6321, 2018 : PubMed ESTHER: Knapp_2018_Sci.Rep_8_6321 PubMedSearch: Knapp 2018 Sci.Rep 8 6321 PubMedID: 29679020 Gene_locus related to this paper: 9pleo-a0a2v1dn29, 9helo-a0a2v1c5l1, 9pleo-a0a2v1dti3, 9helo-a0a2v1bts1, 9helo-a0a2v1cbe5, 9pleo-a0a2v1cxz2, 9pleo-a0a2v1d1n3, 9pleo-a0a2v1db80, 9pleo-a0a2v1ddg5, 9pleo-a0a2v1dij1, 9pleo-a0a2v1dp20, 9pleo-a0a2v1e6x2, 9pleo-a0a2v1ee64, 9helo-a0a2v1cbn2, 9helo-a0a2v1b581, 9pleo-a0a2v1e5g2, corcc-a0a2t2nt04, 9helo-a0a2v1buk5 Abstract Dark septate endophytes (DSE) are a form-group of root endophytic fungi with elusive functions. Here, the genomes of two common DSE of semiarid areas, Cadophora sp. and Periconia macrospinosa were sequenced and analyzed with another 32 ascomycetes of different lifestyles. Cadophora sp. (Helotiales) and P. macrospinosa (Pleosporales) have genomes of 70.46 Mb and 54.99 Mb with 22,766 and 18,750 gene models, respectively. The majority of DSE-specific protein clusters lack functional annotation with no similarity to characterized proteins, implying that they have evolved unique genetic innovations. Both DSE possess an expanded number of carbohydrate active enzymes (CAZymes), including plant cell wall degrading enzymes (PCWDEs). Those were similar in three other DSE, and contributed a signal for the separation of root endophytes in principal component analyses of CAZymes, indicating shared genomic traits of DSE fungi. Number of secreted proteases and lipases, aquaporins, and genes linked to melanin synthesis were also relatively high in our fungi. In spite of certain similarities between our two DSE, we observed low levels of convergence in their gene family evolution. This suggests that, despite originating from the same habitat, these two fungi evolved along different evolutionary trajectories and display considerable functional differences within the endophytic lifestyle. Title: Fungi Contribute Critical but Spatially Varying Roles in Nitrogen and Carbon Cycling in Acid Mine Drainage Mosier AC, Miller CS, Frischkorn KR, Ohm RA, Li Z, LaButti K, Lapidus A, Lipzen A, Chen C and Banfield JF <6 more author(s)> Mosier AC, Miller CS, Frischkorn KR, Ohm RA, Li Z, LaButti K, Lapidus A, Lipzen A, Chen C, Johnson J, Lindquist EA, Pan C, Hettich RL, Grigoriev IV, Singer SW, Banfield JF (- 6) Ref: Front Microbiol, 7:238, 2016 : PubMed ESTHER: Mosier_2016_Front.Microbiol_7_238 PubMedSearch: Mosier 2016 Front.Microbiol 7 238 PubMedID: 26973616 Gene_locus related to this paper: 9pezi-a0a150vf31, 9pezi-a0a150uua7, 9pezi-a0a150uvr8, 9pezi-a0a150uzg0, 9pezi-a0a150v0d4, 9pezi-a0a150v5h7, 9pezi-a0a150v662, 9pezi-a0a150v8z3, 9pezi-a0a150v9v5, 9pezi-a0a150vc68, 9pezi-a0a150vcp1, 9pezi-a0a150vd70, 9pezi-a0a150vda0, 9pezi-a0a150vgv5, 9pezi-a0a150vil1, 9pezi-a0a150uu68, 9pezi-a0a150vas8, 9pezi-a0a150vji1, 9pezi-a0a150vii2 Abstract The ecosystem roles of fungi have been extensively studied by targeting one organism and/or biological process at a time, but the full metabolic potential of fungi has rarely been captured in an environmental context. We hypothesized that fungal genome sequences could be assembled directly from the environment using metagenomics and that transcriptomics and proteomics could simultaneously reveal metabolic differentiation across habitats. We reconstructed the near-complete 27 Mbp genome of a filamentous fungus, Acidomyces richmondensis, and evaluated transcript and protein expression in floating and streamer biofilms from an acid mine drainage (AMD) system. A. richmondensis transcripts involved in denitrification and in the degradation of complex carbon sources (including cellulose) were up-regulated in floating biofilms, whereas central carbon metabolism and stress-related transcripts were significantly up-regulated in streamer biofilms. These findings suggest that the biofilm niches are distinguished by distinct carbon and nitrogen resource utilization, oxygen availability, and environmental challenges. An isolated A. richmondensis strain from this environment was used to validate the metagenomics-derived genome and confirm nitrous oxide production at pH 1. Overall, our analyses defined mechanisms of fungal adaptation and identified a functional shift related to different roles in carbon and nitrogen turnover for the same species of fungi growing in closely located but distinct biofilm niches. Title: The genomic substrate for adaptive radiation in African cichlid fish Brawand D, Wagner CE, Li YI, Malinsky M, Keller I, Fan S, Simakov O, Ng AY, Lim ZW and Di Palma F <65 more author(s)> Brawand D, Wagner CE, Li YI, Malinsky M, Keller I, Fan S, Simakov O, Ng AY, Lim ZW, Bezault E, Turner-Maier J, Johnson J, Alcazar R, Noh HJ, Russell P, Aken B, Alfoldi J, Amemiya C, Azzouzi N, Baroiller JF, Barloy-Hubler F, Berlin A, Bloomquist R, Carleton KL, Conte MA, D'Cotta H, Eshel O, Gaffney L, Galibert F, Gante HF, Gnerre S, Greuter L, Guyon R, Haddad NS, Haerty W, Harris RM, Hofmann HA, Hourlier T, Hulata G, Jaffe DB, Lara M, Lee AP, MacCallum I, Mwaiko S, Nikaido M, Nishihara H, Ozouf-Costaz C, Penman DJ, Przybylski D, Rakotomanga M, Renn SC, Ribeiro FJ, Ron M, Salzburger W, Sanchez-Pulido L, Santos ME, Searle S, Sharpe T, Swofford R, Tan FJ, Williams L, Young S, Yin S, Okada N, Kocher TD, Miska EA, Lander ES, Venkatesh B, Fernald RD, Meyer A, Ponting CP, Streelman JT, Lindblad-Toh K, Seehausen O, Di Palma F (- 65) Ref: Nature, 513:375, 2014 : PubMed ESTHER: Brawand_2014_Nature_513_375 PubMedSearch: Brawand 2014 Nature 513 375 PubMedID: 25186727 Gene_locus related to this paper: oreni-i3j014, oreni-i3iw22, oreni-i3iwp5, oreni-i3j6k7, oreni-i3jhp1, oreni-i3jeq5, oreni-i3kf65, oreni-i3j210, oreni-i3j221, oreni-i3k9y3, oreni-i3k5p0, oreni-i3jwi4, oreni-i3jv26, oreni-i3k9m0, 9cich-a0a3p9d5c0, oreni-i3knk8, 9cich-a0a3b4hcr5, 9cich-a0a3p9dbr8, oreni-i3k1a6, oreni-i3jq62, 9cich-a0a3p9dgm2, neobr-a0a3q4g2a1, oreni-i3jdv9, neobr-a0a3q4hk25, oreni-i3jbm3, oreni-i3jbm2, oreni-i3jds8, 9cich-a0a3b4hbf8, 9cich-a0a3p9ars6, neobr-a0a3q4ghw9, oreni-i3kx89, 9cich-a0a3p9d359, oreni-i3kaa3 Abstract Cichlid fishes are famous for large, diverse and replicated adaptive radiations in the Great Lakes of East Africa. To understand the molecular mechanisms underlying cichlid phenotypic diversity, we sequenced the genomes and transcriptomes of five lineages of African cichlids: the Nile tilapia (Oreochromis niloticus), an ancestral lineage with low diversity; and four members of the East African lineage: Neolamprologus brichardi/pulcher (older radiation, Lake Tanganyika), Metriaclima zebra (recent radiation, Lake Malawi), Pundamilia nyererei (very recent radiation, Lake Victoria), and Astatotilapia burtoni (riverine species around Lake Tanganyika). We found an excess of gene duplications in the East African lineage compared to tilapia and other teleosts, an abundance of non-coding element divergence, accelerated coding sequence evolution, expression divergence associated with transposable element insertions, and regulation by novel microRNAs. In addition, we analysed sequence data from sixty individuals representing six closely related species from Lake Victoria, and show genome-wide diversifying selection on coding and regulatory variants, some of which were recruited from ancient polymorphisms. We conclude that a number of molecular mechanisms shaped East African cichlid genomes, and that amassing of standing variation during periods of relaxed purifying selection may have been important in facilitating subsequent evolutionary diversification. Title: The genome of the green anole lizard and a comparative analysis with birds and mammals Alfoldi J, Di Palma F, Grabherr M, Williams C, Kong L, Mauceli E, Russell P, Lowe CB, Glor RE and Lindblad-Toh K <40 more author(s)> Alfoldi J, Di Palma F, Grabherr M, Williams C, Kong L, Mauceli E, Russell P, Lowe CB, Glor RE, Jaffe JD, Ray DA, Boissinot S, Shedlock AM, Botka C, Castoe TA, Colbourne JK, Fujita MK, Moreno RG, ten Hallers BF, Haussler D, Heger A, Heiman D, Janes DE, Johnson J, de Jong PJ, Koriabine MY, Lara M, Novick PA, Organ CL, Peach SE, Poe S, Pollock DD, de Queiroz K, Sanger T, Searle S, Smith JD, Smith Z, Swofford R, Turner-Maier J, Wade J, Young S, Zadissa A, Edwards SV, Glenn TC, Schneider CJ, Losos JB, Lander ES, Breen M, Ponting CP, Lindblad-Toh K (- 40) Ref: Nature, 477:587, 2011 : PubMed ESTHER: Alfoldi_2011_Nature_477_587 PubMedSearch: Alfoldi 2011 Nature 477 587 PubMedID: 21881562 Gene_locus related to this paper: anoca-h9g670, anoca-h9g675, anoca-h9g680, anoca-h9gbf2, anoca-h9gl37, anoca-h9gq07, anoca-h9gqa2, anoca-h9gqv4, anoca-h9gr08, anoca-h9glr3, anoca-h9gfq0, anoca-h9gfy1, anoca-h9g7n4, anoca-h9gpa2, anoca-h9g3p8 Abstract The evolution of the amniotic egg was one of the great evolutionary innovations in the history of life, freeing vertebrates from an obligatory connection to water and thus permitting the conquest of terrestrial environments. Among amniotes, genome sequences are available for mammals and birds, but not for non-avian reptiles. Here we report the genome sequence of the North American green anole lizard, Anolis carolinensis. We find that A. carolinensis microchromosomes are highly syntenic with chicken microchromosomes, yet do not exhibit the high GC and low repeat content that are characteristic of avian microchromosomes. Also, A. carolinensis mobile elements are very young and diverse-more so than in any other sequenced amniote genome. The GC content of this lizard genome is also unusual in its homogeneity, unlike the regionally variable GC content found in mammals and birds. We describe and assign sequence to the previously unknown A. carolinensis X chromosome. Comparative gene analysis shows that amniote egg proteins have evolved significantly more rapidly than other proteins. An anole phylogeny resolves basal branches to illuminate the history of their repeated adaptive radiations. Title: Draft genome sequence of the chemolithoheterotrophic, halophilic methylotroph Methylophaga thiooxydans DMS010 Boden R, Ferriera S, Johnson J, Kelly DP, Murrell JC, Schafer H Ref: Journal of Bacteriology, 193:3154, 2011 : PubMed ESTHER: Boden_2011_J.Bacteriol_193_3154 PubMedSearch: Boden 2011 J.Bacteriol 193 3154 PubMedID: 21478352 Abstract Methylophaga thiooxydans is a mesophilic, obligately halophilic bacterium that is capable of methylotrophic growth on a range of one-carbon compounds as well as chemolithoheterotrophic growth at the expense of thiosulfate. Here we present the draft genome sequence of Methylophaga thiooxydans DMS010 (DSM 22068(T), VKM B2586(T)), the type strain of the species, which has allowed prediction of the genes involved in one-carbon metabolism, nitrogen metabolism, and other aspects of central metabolism. Title: Concomitant use of cholinesterase inhibitors and anticholinergics: prevalence and outcomes Boudreau DM, Yu O, Gray SL, Raebel MA, Johnson J, Larson EB Ref: J Am Geriatr Soc, 59:2069, 2011 : PubMed ESTHER: Boudreau_2011_J.Am.Geriatr.Soc_59_2069 PubMedSearch: Boudreau 2011 J.Am.Geriatr.Soc 59 2069 PubMedID: 22091958 Abstract OBJECTIVES: To determine the extent of concomitant use of cholinesterase inhibitor (ChI) and anticholinergic (ACh) medications and the clinical consequences of dual use in a population-based setting. DESIGN: Retrospective cohort study. SETTING: Group Health Cooperative and Kaiser Permanente Colorado. PARTICIPANTS: Five thousand six hundred twenty-five adults aged 50 and older who began new use of a ChI between 2000 and 2007. MEASUREMENTS: Rates and characteristics of concomitant ChI and ACh use and the association between dual use and the outcomes of death and nursing home placement (claim from a nursing home with no prior claims used as a proxy). RESULTS: Thirty-seven percent of ChI users also received AChs. Eleven percent of ChI users were concomitantly using two or more moderate to potent AChs. Median duration of this concomitant use was approximately 4 months, but a substantial proportion (25%) continued to use both medication classes simultaneously for longer than 12 months. In 23% of ChI users, AChs were being used at the time ChI therapy was initiated. The majority of this ACh use (77%) was not stopped once ChIs were started. No association was observed between concomitant use and risk of death or nursing home placement. CONCLUSION: These results should raise awareness about the prevalence and potential inappropriateness of concomitant use of ChIs and AChs and promote evaluations of practices intended to improve care standards. Title: Draft genome sequence of Caminibacter mediatlanticus strain TB-2, an epsilonproteobacterium isolated from a deep-sea hydrothermal vent Giovannelli D, Ferriera S, Johnson J, Kravitz S, Perez-Rodriguez I, Ricci J, O'Brien C, Voordeckers JW, Bini E, Vetriani C Ref: Stand Genomic Sci, 5:135, 2011 : PubMed ESTHER: Giovannelli_2011_Stand.Genomic.Sci_5_135 PubMedSearch: Giovannelli 2011 Stand.Genomic.Sci 5 135 PubMedID: 22180817 Gene_locus related to this paper: 9prot-a6def3, 9prot-a6da46 Abstract Caminibacter mediatlanticus strain TB-2(T) [1], is a thermophilic, anaerobic, chemolithoautotrophic bacterium, isolated from the walls of an active deep-sea hydrothermal vent chimney on the Mid-Atlantic Ridge and the type strain of the species. C. mediatlanticus is a Gram-negative member of the Epsilonproteobacteria (order Nautiliales) that grows chemolithoautotrophically with H(2) as the energy source and CO(2) as the carbon source. Nitrate or sulfur is used as the terminal electron acceptor, with resulting production of ammonium and hydrogen sulfide, respectively. In view of the widespread distribution, importance and physiological characteristics of thermophilic Epsilonproteobacteria in deep-sea geothermal environments, it is likely that these organisms provide a relevant contribution to both primary productivity and the biogeochemical cycling of carbon, nitrogen and sulfur at hydrothermal vents. Here we report the main features of the genome of C. mediatlanticus strain TB-2(T). Title: Genome sequence of the Marine Janibacter Sp. Strain HTCC2649 Thrash JC, Cho JC, Bertagnolli AD, Ferriera S, Johnson J, Vergin KL, Giovannoni SJ Ref: Journal of Bacteriology, 193:584, 2011 : PubMed ESTHER: Thrash_2011_J.Bacteriol_193_584 PubMedSearch: Thrash 2011 J.Bacteriol 193 584 PubMedID: 21075932 Gene_locus related to this paper: 9mico-a3tmr7, 9mico-a3tg99, 9mico-a3tga0, 9mico-a3thg8, 9mico-a3tjp7, 9mico-a3tmm2, 9mico-a3tn91, 9mico-a3tnk2, 9mico-a3tp75, 9mico-a3tqm4, 9mico-a3trw6, 9mico-a3tgi4, 9mico-a3tg58 Abstract Janibacter sp. strain HTCC2649 is a novel marine member of the Actinobacteria, family Intrasporangiaceae, and is closely related to Janibacter melonis CM2104(T) and Knoellia sinensis HKI 0119(T). The organism was isolated from a sample collected at Hydrostation S south of Bermuda by using high-throughput culturing techniques. Here we present the genome sequence of Janibacter sp. strain HTCC2649. Title: Genome sequences of the human body louse and its primary endosymbiont provide insights into the permanent parasitic lifestyle Kirkness EF, Haas BJ, Sun W, Braig HR, Perotti MA, Clark JM, Lee SH, Robertson HM, Kennedy RC and Pittendrigh BR <61 more author(s)> Kirkness EF, Haas BJ, Sun W, Braig HR, Perotti MA, Clark JM, Lee SH, Robertson HM, Kennedy RC, Elhaik E, Gerlach D, Kriventseva EV, Elsik CG, Graur D, Hill CA, Veenstra JA, Walenz B, Tubio JM, Ribeiro JM, Rozas J, Johnston JS, Reese JT, Popadic A, Tojo M, Raoult D, Reed DL, Tomoyasu Y, Kraus E, Mittapalli O, Margam VM, Li HM, Meyer JM, Johnson RM, Romero-Severson J, Vanzee JP, Alvarez-Ponce D, Vieira FG, Aguade M, Guirao-Rico S, Anzola JM, Yoon KS, Strycharz JP, Unger MF, Christley S, Lobo NF, Seufferheld MJ, Wang N, Dasch GA, Struchiner CJ, Madey G, Hannick LI, Bidwell S, Joardar V, Caler E, Shao R, Barker SC, Cameron S, Bruggner RV, Regier A, Johnson J, Viswanathan L, Utterback TR, Sutton GG, Lawson D, Waterhouse RM, Venter JC, Strausberg RL, Berenbaum MR, Collins FH, Zdobnov EM, Pittendrigh BR (- 61) Ref: Proc Natl Acad Sci U S A, 107:12168, 2010 : PubMed ESTHER: Kirkness_2010_Proc.Natl.Acad.Sci.U.S.A_107_12168 PubMedSearch: Kirkness 2010 Proc.Natl.Acad.Sci.U.S.A 107 12168 PubMedID: 20566863 Gene_locus related to this paper: pedhb-ACHE1, pedhb-ACHE2, pedhc-e0v9b5, pedhc-e0v9b6, pedhc-e0v9b7, pedhc-e0vbv5, pedhc-e0vcd0, pedhc-e0vcl7, pedhc-e0vd69, pedhc-e0ve50, pedhc-e0vel6, pedhc-e0vel7, pedhc-e0vf98, pedhc-e0vfs8, pedhc-e0vfv0, pedhc-e0vg01, pedhc-e0vha2, pedhc-e0vha4, pedhc-e0vi52, pedhc-e0vp42, pedhc-e0vqu6, pedhc-e0vuj9, pedhc-e0vup6, pedhc-e0vv55, pedhc-e0vwv3, pedhc-e0vxf7, pedhc-e0vxg1, pedhc-e0w4a6, pedhc-e0w4c8, pedhc-e0w271, pedhc-e0w444, pedhc-e0vym0, pedhc-e0vdk9, pedhc-e0vk10, pedhc-e0vgw4, pedhc-e0vgw7, pedhc-e0vga1, pedhc-e0w3s1, pedhc-e0vzt2 Abstract As an obligatory parasite of humans, the body louse (Pediculus humanus humanus) is an important vector for human diseases, including epidemic typhus, relapsing fever, and trench fever. Here, we present genome sequences of the body louse and its primary bacterial endosymbiont Candidatus Riesia pediculicola. The body louse has the smallest known insect genome, spanning 108 Mb. Despite its status as an obligate parasite, it retains a remarkably complete basal insect repertoire of 10,773 protein-coding genes and 57 microRNAs. Representing hemimetabolous insects, the genome of the body louse thus provides a reference for studies of holometabolous insects. Compared with other insect genomes, the body louse genome contains significantly fewer genes associated with environmental sensing and response, including odorant and gustatory receptors and detoxifying enzymes. The unique architecture of the 18 minicircular mitochondrial chromosomes of the body louse may be linked to the loss of the gene encoding the mitochondrial single-stranded DNA binding protein. The genome of the obligatory louse endosymbiont Candidatus Riesia pediculicola encodes less than 600 genes on a short, linear chromosome and a circular plasmid. The plasmid harbors a unique arrangement of genes required for the synthesis of pantothenate, an essential vitamin deficient in the louse diet. The human body louse, its primary endosymbiont, and the bacterial pathogens that it vectors all possess genomes reduced in size compared with their free-living close relatives. Thus, the body louse genome project offers unique information and tools to use in advancing understanding of coevolution among vectors, symbionts, and pathogens. Title: A catalog of reference genomes from the human microbiome Nelson KE, Weinstock GM, Highlander SK, Worley KC, Creasy HH, Wortman JR, Rusch DB, Mitreva M, Sodergren E and Zhu D <73 more author(s)> Nelson KE, Weinstock GM, Highlander SK, Worley KC, Creasy HH, Wortman JR, Rusch DB, Mitreva M, Sodergren E, Chinwalla AT, Feldgarden M, Gevers D, Haas BJ, Madupu R, Ward DV, Birren BW, Gibbs RA, Methe B, Petrosino JF, Strausberg RL, Sutton GG, White OR, Wilson RK, Durkin S, Giglio MG, Gujja S, Howarth C, Kodira CD, Kyrpides N, Mehta T, Muzny DM, Pearson M, Pepin K, Pati A, Qin X, Yandava C, Zeng Q, Zhang L, Berlin AM, Chen L, Hepburn TA, Johnson J, McCorrison J, Miller J, Minx P, Nusbaum C, Russ C, Sykes SM, Tomlinson CM, Young S, Warren WC, Badger J, Crabtree J, Markowitz VM, Orvis J, Cree A, Ferriera S, Fulton LL, Fulton RS, Gillis M, Hemphill LD, Joshi V, Kovar C, Torralba M, Wetterstrand KA, Abouellleil A, Wollam AM, Buhay CJ, Ding Y, Dugan S, Fitzgerald MG, Holder M, Hostetler J, Clifton SW, Allen-Vercoe E, Earl AM, Farmer CN, Liolios K, Surette MG, Xu Q, Pohl C, Wilczek-Boney K, Zhu D (- 73) Ref: Science, 328:994, 2010 : PubMed ESTHER: Nelson_2010_Science_328_994 PubMedSearch: Nelson 2010 Science 328 994 PubMedID: 20489017 Gene_locus related to this paper: strp2-q04l35, strpn-AXE1, strpn-pepx Abstract The human microbiome refers to the community of microorganisms, including prokaryotes, viruses, and microbial eukaryotes, that populate the human body. The National Institutes of Health launched an initiative that focuses on describing the diversity of microbial species that are associated with health and disease. The first phase of this initiative includes the sequencing of hundreds of microbial reference genomes, coupled to metagenomic sequencing from multiple body sites. Here we present results from an initial reference genome sequencing of 178 microbial genomes. From 547,968 predicted polypeptides that correspond to the gene complement of these strains, previously unidentified ("novel") polypeptides that had both unmasked sequence length greater than 100 amino acids and no BLASTP match to any nonreference entry in the nonredundant subset were defined. This analysis resulted in a set of 30,867 polypeptides, of which 29,987 (approximately 97%) were unique. In addition, this set of microbial genomes allows for approximately 40% of random sequences from the microbiome of the gastrointestinal tract to be associated with organisms based on the match criteria used. Insights into pan-genome analysis suggest that we are still far from saturating microbial species genetic data sets. In addition, the associated metrics and standards used by our group for quality assurance are presented. Title: Genome sequences of strains HTCC2148 and HTCC2080, belonging to the OM60/NOR5 clade of the Gammaproteobacteria Thrash JC, Cho JC, Ferriera S, Johnson J, Vergin KL, Giovannoni SJ Ref: Journal of Bacteriology, 192:3842, 2010 : PubMed ESTHER: Thrash_2010_J.Bacteriol_192_3842 PubMedSearch: Thrash 2010 J.Bacteriol 192 3842 PubMedID: 20472793 Gene_locus related to this paper: 9gamm-a0z1c5, 9gamm-a0z1f5, 9gamm-a0z2s0, 9gamm-a0z3u8, 9gamm-a0z4a8, 9gamm-a0z4j5, 9gamm-a0z5h2, 9gamm-a0z5n0, 9gamm-a0z6e4, 9gamm-a0z8c8, 9gamm-a0z329, 9gamm-a0z514, 9gamm-a0z518, 9gamm-a0z640, 9gamm-a0z4z1, 9gamm-a0z4j2, 9gamm-b7s1l3, 9gamm-a0z507, 9gamm-b7rum6, 9gamm-b7ry27, 9gamm-b7rxk5, 9gamm-a0z6c3 Abstract Organisms in the OM60/NOR5 clade of the Gammaproteobacteria are ubiquitous in the world's oceans and can make up as much as 11% of bacterial cells in certain areas. Isolated from coastal Oregon water, Gammaproteobacteria HTCC2148 and HTCC2080 are two members of this important clade. Here we present the genome sequences of the OM60 Gammaproteobacteria HTCC2148 and HTCC2080. Title: Genome sequences of Pelagibaca bermudensis HTCC2601T and Maritimibacter alkaliphilus HTCC2654T, the type strains of two marine Roseobacter genera Thrash JC, Cho JC, Ferriera S, Johnson J, Vergin KL, Giovannoni SJ Ref: Journal of Bacteriology, 192:5552, 2010 : PubMed ESTHER: Thrash_2010_J.Bacteriol_192_5552 PubMedSearch: Thrash 2010 J.Bacteriol 192 5552 PubMedID: 20729358 Gene_locus related to this paper: 9rhob-a3va73, 9rhob-a3vae5, 9rhob-a3vby9, 9rhob-a3vd43, 9rhob-a3vde0, 9rhob-a3vdm3, 9rhob-a3vdy3, 9rhob-a3ve12, 9rhob-a3vhg2, 9rhob-a3vhi4, 9rhob-a3vi32, 9rhob-a3vjf9, 9rhob-a3vl43, 9rhob-a3vl64, 9rhob-a3vlh4, 9rhob-a3vm86, 9rhob-q0fk06, 9rhob-q0flx2, 9rhob-q0fmy2, 9rhob-q0fmz2, 9rhob-q0fnb8, 9rhob-q0fsb4, 9rhob-q0fv60, pelbh-q0fmy5, pelbh-q0fp89, 9rhob-a3vji7 Abstract Pelagibaca bermudensis HTCC2601(T) and Maritimibacter alkaliphilus HTCC2654(T) represent two marine genera in the globally significant Roseobacter clade of the Alphaproteobacteria. Here, we present the genome sequences of these organisms, isolated from the Sargasso Sea using dilution-to-extinction culturing, which offer insight into the genetic basis for the metabolic and ecological diversity of this important group. Title: Safety and tolerability of sitagliptin in clinical studies: a pooled analysis of data from 10,246 patients with type 2 diabetes Williams-Herman D, Engel SS, Round E, Johnson J, Golm GT, Guo H, Musser BJ, Davies MJ, Kaufman KD, Goldstein BJ Ref: BMC Endocr Disord, 10:7, 2010 : PubMed ESTHER: Williams-Herman_2010_BMC.Endocr.Disord_10_7 PubMedSearch: Williams-Herman 2010 BMC.Endocr.Disord 10 7 PubMedID: 20412573 Abstract BACKGROUND: In a previous pooled analysis of 12 double-blind clinical studies that included data on 6,139 patients with type 2 diabetes, treatment with sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, was shown to be generally well tolerated compared with treatment with control agents. As clinical development of sitagliptin continues, additional studies have been completed, and more patients have been exposed to sitagliptin. The purpose of the present analysis is to update the safety and tolerability assessment of sitagliptin by pooling data from 19 double-blind clinical studies. METHODS: The present analysis included data from 10,246 patients with type 2 diabetes who received either sitagliptin 100 mg/day (N = 5,429; sitagliptin group) or a comparator agent (placebo or an active comparator) (N = 4,817; non-exposed group). The 19 studies from which this pooled population was drawn represent the double-blind, randomized studies that included patients treated with the usual clinical dose of sitagliptin (100 mg/day) for between 12 weeks and 2 years and for which results were available as of July 2009. These 19 studies assessed sitagliptin taken as monotherapy, initial combination therapy with metformin or pioglitazone, or as add-on combination therapy with other antihyperglycemic agents (metformin, pioglitazone, a sulfonylurea +/- metformin, insulin +/- metformin, or rosiglitazone + metformin). Patients in the non-exposed group were taking placebo, metformin, pioglitazone, a sulfonylurea +/- metformin, insulin +/- metformin, or rosiglitazone + metformin. The analysis used patient-level data from each study to evaluate between-group differences in the exposure-adjusted incidence rates of adverse events. RESULTS: Summary measures of overall adverse events were similar in the sitagliptin and non-exposed groups, except for an increased incidence of drug-related adverse events in the non-exposed group. Incidence rates of specific adverse events were also generally similar between the two groups, except for increased incidence rates of hypoglycemia, related to the greater use of a sulfonylurea, and diarrhea, related to the greater use of metformin, in the non-exposed group and constipation in the sitagliptin group. Treatment with sitagliptin was not associated with an increased risk of major adverse cardiovascular events. CONCLUSIONS: In this updated pooled safety analysis of data from 10,246 patients with type 2 diabetes, sitagliptin 100 mg/day was generally well tolerated in clinical trials of up to 2 years in duration. Title: The genomic basis of trophic strategy in marine bacteria Lauro FM, McDougald D, Thomas T, Williams TJ, Egan S, Rice S, DeMaere MZ, Ting L, Ertan H and Cavicchioli R <11 more author(s)> Lauro FM, McDougald D, Thomas T, Williams TJ, Egan S, Rice S, DeMaere MZ, Ting L, Ertan H, Johnson J, Ferriera S, Lapidus A, Anderson I, Kyrpides N, Munk AC, Detter C, Han CS, Brown MV, Robb FT, Kjelleberg S, Cavicchioli R (- 11) Ref: Proc Natl Acad Sci U S A, 106:15527, 2009 : PubMed ESTHER: Lauro_2009_Proc.Natl.Acad.Sci.U.S.A_106_15527 PubMedSearch: Lauro 2009 Proc.Natl.Acad.Sci.U.S.A 106 15527 PubMedID: 19805210 Gene_locus related to this paper: phoas-q1zm99, phoas-q1zpt1, phoas-q1zwh7, phoas-q1zx01, phoas-q1zlj9, sphal-q1grs6 Abstract Many marine bacteria have evolved to grow optimally at either high (copiotrophic) or low (oligotrophic) nutrient concentrations, enabling different species to colonize distinct trophic habitats in the oceans. Here, we compare the genome sequences of two bacteria, Photobacterium angustum S14 and Sphingopyxis alaskensis RB2256, that serve as useful model organisms for copiotrophic and oligotrophic modes of life and specifically relate the genomic features to trophic strategy for these organisms and define their molecular mechanisms of adaptation. We developed a model for predicting trophic lifestyle from genome sequence data and tested >400,000 proteins representing >500 million nucleotides of sequence data from 126 genome sequences with metagenome data of whole environmental samples. When applied to available oceanic metagenome data (e.g., the Global Ocean Survey data) the model demonstrated that oligotrophs, and not the more readily isolatable copiotrophs, dominate the ocean's free-living microbial populations. Using our model, it is now possible to define the types of bacteria that specific ocean niches are capable of sustaining. Title: Complete genome sequence of Erythrobacter litoralis HTCC2594 Oh HM, Giovannoni SJ, Ferriera S, Johnson J, Cho JC Ref: Journal of Bacteriology, 191:2419, 2009 : PubMed ESTHER: Oh_2009_J.Bacteriol_191_2419 PubMedSearch: Oh 2009 J.Bacteriol 191 2419 PubMedID: 19168610 Gene_locus related to this paper: eryhl-Q2N8C6, erylh-q2n7g7, erylh-q2n9y4, erylh-q2ncg0, erylh-q2nd60, erylh-q2na21 Abstract Erythrobacter litoralis has been known as a bacteriochlorophyll a-containing, aerobic, anoxygenic, phototrophic bacterium. Here we announce the complete genome sequence of E. litoralis HTCC2594, which is devoid of phototrophic potential. E. litoralis HTCC2594, isolated by dilution-to-extinction culturing from seawater, could not carry out aerobic anoxygenic phototrophy and lacked genes for bacteriochlorophyll a biosynthesis and photosynthetic reaction center proteins. Title: Complete genome sequence of Robiginitalea biformata HTCC2501 Oh HM, Giovannoni SJ, Lee K, Ferriera S, Johnson J, Cho JC Ref: Journal of Bacteriology, 191:7144, 2009 : PubMed ESTHER: Oh_2009_J.Bacteriol_191_7144 PubMedSearch: Oh 2009 J.Bacteriol 191 7144 PubMedID: 19767438 Gene_locus related to this paper: robbh-a4cgq6, robbh-a4cil9, robbh-a4cir1, robbh-a4cj93, robbh-a4cje2, robbh-a4cjy8, robbh-a4cjz4, robbh-a4ck49, robbh-a4ckw4, robbh-a4cli1, robbh-a4cme1, robbh-a4cmz6, robbh-a4cq56 Abstract Robiginitalea biformata HTCC2501, isolated from the Sargasso Sea by dilution-to-extinction culturing, has been known as an aerobic chemoheterotroph with carotenoid pigments and dimorphic growth phases. Here, we announce the complete sequence of the R. biformata HTCC2501 genome, which contains genes for carotenoid biosynthesis and several macromolecule-degrading enzymes. Title: Complete and draft genome sequences of six members of the Aquificales Reysenbach AL, Hamamura N, Podar M, Griffiths E, Ferreira S, Hochstein R, Heidelberg J, Johnson J, Mead D and Voytek MA <4 more author(s)> Reysenbach AL, Hamamura N, Podar M, Griffiths E, Ferreira S, Hochstein R, Heidelberg J, Johnson J, Mead D, Pohorille A, Sarmiento M, Schweighofer K, Seshadri R, Voytek MA (- 4) Ref: Journal of Bacteriology, 191:1992, 2009 : PubMed ESTHER: Reysenbach_2009_J.Bacteriol_191_1992 PubMedSearch: Reysenbach 2009 J.Bacteriol 191 1992 PubMedID: 19136599 Gene_locus related to this paper: hyds0-b4u8t4, hyds0-b4u654, permh-c0qrw4, permh-c0qsh2, sulaa-c1dud5, sulaa-c1dw76, sulsy-b2v6x0, sulsy-b2v7r8, permh-c0qr46, permh-c0qqk7, sulaa-c1dxm2, sulsy-b2v8e9 Abstract The Aquificales are widespread in marine and terrestrial hydrothermal environments. Here, we report the complete and draft genome sequences of six new members of the Aquificales: two marine species, Persephonella marina strain EX-H1 and Hydrogenivirga strain 128-5-R1 (from the East Pacific Rise, 9 degrees 50.3'N, 104 degrees 17.5'W, and the Eastern Lau Spreading Center, 176 degrees 11.5'W, 20 degrees 45.8'S, respectively), and four terrestrial isolates, Sulfurihydrogenibium azorense strain Az-Fu1, Sulfurihydrogenibium yellowstonense strain SS-5, and Sulfurihydrogenibium strain Y03AOP1 (from Furnas, Azores, Portugal, and Calcite Springs and Obsidian Pool in Yellowstone National Park, United States, respectively), and the only thermoacidophilic isolate, Hydrogenobaculum strain Y04AAS1 (from a stream adjacent to Obsidian Pool). Significant differences among the different species exist that include nitrogen metabolism, hydrogen utilization, chemotaxis, and signal transduction, providing insights into their ecological niche adaptations. Title: Organised genome dynamics in the Escherichia coli species results in highly diverse adaptive paths Touchon M, Hoede C, Tenaillon O, Barbe V, Baeriswyl S, Bidet P, Bingen E, Bonacorsi S, Bouchier C and Denamur E <31 more author(s)> Touchon M, Hoede C, Tenaillon O, Barbe V, Baeriswyl S, Bidet P, Bingen E, Bonacorsi S, Bouchier C, Bouvet O, Calteau A, Chiapello H, Clermont O, Cruveiller S, Danchin A, Diard M, Dossat C, Karoui ME, Frapy E, Garry L, Ghigo JM, Gilles AM, Johnson J, Le Bouguenec C, Lescat M, Mangenot S, Martinez-Jehanne V, Matic I, Nassif X, Oztas S, Petit MA, Pichon C, Rouy Z, Ruf CS, Schneider D, Tourret J, Vacherie B, Vallenet D, Medigue C, Rocha EP, Denamur E (- 31) Ref: PLoS Genet, 5:e1000344, 2009 : PubMed ESTHER: Touchon_2009_PLoS.Genet_5_E1000344 PubMedSearch: Touchon 2009 PLoS.Genet 5 E1000344 PubMedID: 19165319 Gene_locus related to this paper: ecoli-Aes, ecoli-rutD, ecoli-bioh, ecoli-C0410, ecoli-C2429, ecoli-C3633, ecoli-C3636, ecoli-C4836, ecoli-d7xp23, ecoli-dlhh, ecoli-entf, ecoli-fes, ecoli-IROD, ecoli-IROE, ecoli-mhpc, ecoli-pldb, ecoli-ptrb, ecoli-yafa, ecoli-yaim, ecoli-ybff, ecoli-ycfp, ecoli-ycjy, ecoli-yeiG, ecoli-YFBB, ecoli-yghX, ecoli-yhet, ecoli-yiel, ecoli-yjfp, ecoli-YNBC, ecoli-ypfh, ecoli-ypt1, ecoli-yqia, ecoli-Z0347, ecoli-Z1930, ecoli-YfhR, ecout-q1r7l6, escfe-e9z855, yerpe-YBTT, ecolx-e0qx45 Abstract The Escherichia coli species represents one of the best-studied model organisms, but also encompasses a variety of commensal and pathogenic strains that diversify by high rates of genetic change. We uniformly (re-) annotated the genomes of 20 commensal and pathogenic E. coli strains and one strain of E. fergusonii (the closest E. coli related species), including seven that we sequenced to completion. Within the approximately 18,000 families of orthologous genes, we found approximately 2,000 common to all strains. Although recombination rates are much higher than mutation rates, we show, both theoretically and using phylogenetic inference, that this does not obscure the phylogenetic signal, which places the B2 phylogenetic group and one group D strain at the basal position. Based on this phylogeny, we inferred past evolutionary events of gain and loss of genes, identifying functional classes under opposite selection pressures. We found an important adaptive role for metabolism diversification within group B2 and Shigella strains, but identified few or no extraintestinal virulence-specific genes, which could render difficult the development of a vaccine against extraintestinal infections. Genome flux in E. coli is confined to a small number of conserved positions in the chromosome, which most often are not associated with integrases or tRNA genes. Core genes flanking some of these regions show higher rates of recombination, suggesting that a gene, once acquired by a strain, spreads within the species by homologous recombination at the flanking genes. Finally, the genome's long-scale structure of recombination indicates lower recombination rates, but not higher mutation rates, at the terminus of replication. The ensuing effect of background selection and biased gene conversion may thus explain why this region is A+T-rich and shows high sequence divergence but low sequence polymorphism. Overall, despite a very high gene flow, genes co-exist in an organised genome. Title: Comparative genomics of two ecotypes of the marine planktonic copiotroph Alteromonas macleodii suggests alternative lifestyles associated with different kinds of particulate organic matter Ivars-Martinez E, Martin-Cuadrado AB, D'Auria G, Mira A, Ferriera S, Johnson J, Friedman R, Rodriguez-Valera F Ref: Isme J, 2:1194, 2008 : PubMed ESTHER: Ivars-Martinez_2008_ISME.J_2_1194 PubMedSearch: Ivars-Martinez 2008 ISME.J 2 1194 PubMedID: 18670397 Gene_locus related to this paper: altmd-f2gbn3, altmb-k0e9i0, altma-s5blx4, altmd-f2g7m7, altma-j9y8r9, altma-j9ycg2, altma-s5cfn7, altma-j9yd23, altma-s5ahd5 Abstract Alteromonas macleodii is a common marine heterotrophic gamma-proteobacterium. Isolates from this microbe cluster by molecular analysis into two major genotypic groups or ecotypes, one found in temperate latitudes in the upper water column and another that is for the most part found in the deep water column of the Mediterranean. Here, we describe the genome of one strain of the 'deep ecotype' (AltDE) isolated from 1000 m in the Eastern Mediterranean and compare this genome with that of the type strain ATCC 27126, a representative of the global 'surface' ecotype. The genomes are substantially different with DNA sequence similarity values that are borderline for microbes belonging to the same species, and a large differential gene content, mainly found in islands larger than 20 kbp, that also recruit poorly to the Global Ocean Sampling project (GOS). These genomic differences indicate that AltDE is probably better suited to microaerophilic conditions and for the degradation of recalcitrant compounds such as urea. These, together with other features, and the distribution of this genotypic group, indicate that this microbe colonizes relatively large particles that sink rapidly to meso and bathypelagic depths. The genome of ATCC 27126 on the other hand has more potential for regulation (two component systems) and degrades more sugars and amino acids, which is consistent with a more transient particle attachment, as would be expected for lineages specialized in colonizing smaller particulate organic matter with much slower sinking rates. The genomic data are also consistent with a picture of incipient speciation driven by niche specialization. Title: Evolution of genes and genomes on the Drosophila phylogeny Clark AG, Eisen MB, Smith DR, Bergman CM, Oliver B, Markow TA, Kaufman TC, Kellis M, Gelbart W and MacCallum I <405 more author(s)> Clark AG, Eisen MB, Smith DR, Bergman CM, Oliver B, Markow TA, Kaufman TC, Kellis M, Gelbart W, Iyer VN, Pollard DA, Sackton TB, Larracuente AM, Singh ND, Abad JP, Abt DN, Adryan B, Aguade M, Akashi H, Anderson WW, Aquadro CF, Ardell DH, Arguello R, Artieri CG, Barbash DA, Barker D, Barsanti P, Batterham P, Batzoglou S, Begun D, Bhutkar A, Blanco E, Bosak SA, Bradley RK, Brand AD, Brent MR, Brooks AN, Brown RH, Butlin RK, Caggese C, Calvi BR, Bernardo de Carvalho A, Caspi A, Castrezana S, Celniker SE, Chang JL, Chapple C, Chatterji S, Chinwalla A, Civetta A, Clifton SW, Comeron JM, Costello JC, Coyne JA, Daub J, David RG, Delcher AL, Delehaunty K, Do CB, Ebling H, Edwards K, Eickbush T, Evans JD, Filipski A, Findeiss S, Freyhult E, Fulton L, Fulton R, Garcia AC, Gardiner A, Garfield DA, Garvin BE, Gibson G, Gilbert D, Gnerre S, Godfrey J, Good R, Gotea V, Gravely B, Greenberg AJ, Griffiths-Jones S, Gross S, Guigo R, Gustafson EA, Haerty W, Hahn MW, Halligan DL, Halpern AL, Halter GM, Han MV, Heger A, Hillier L, Hinrichs AS, Holmes I, Hoskins RA, Hubisz MJ, Hultmark D, Huntley MA, Jaffe DB, Jagadeeshan S, Jeck WR, Johnson J, Jones CD, Jordan WC, Karpen GH, Kataoka E, Keightley PD, Kheradpour P, Kirkness EF, Koerich LB, Kristiansen K, Kudrna D, Kulathinal RJ, Kumar S, Kwok R, Lander E, Langley CH, Lapoint R, Lazzaro BP, Lee SJ, Levesque L, Li R, Lin CF, Lin MF, Lindblad-Toh K, Llopart A, Long M, Low L, Lozovsky E, Lu J, Luo M, Machado CA, Makalowski W, Marzo M, Matsuda M, Matzkin L, McAllister B, McBride CS, McKernan B, McKernan K, Mendez-Lago M, Minx P, Mollenhauer MU, Montooth K, Mount SM, Mu X, Myers E, Negre B, Newfeld S, Nielsen R, Noor MA, O'Grady P, Pachter L, Papaceit M, Parisi MJ, Parisi M, Parts L, Pedersen JS, Pesole G, Phillippy AM, Ponting CP, Pop M, Porcelli D, Powell JR, Prohaska S, Pruitt K, Puig M, Quesneville H, Ram KR, Rand D, Rasmussen MD, Reed LK, Reenan R, Reily A, Remington KA, Rieger TT, Ritchie MG, Robin C, Rogers YH, Rohde C, Rozas J, Rubenfield MJ, Ruiz A, Russo S, Salzberg SL, Sanchez-Gracia A, Saranga DJ, Sato H, Schaeffer SW, Schatz MC, Schlenke T, Schwartz R, Segarra C, Singh RS, Sirot L, Sirota M, Sisneros NB, Smith CD, Smith TF, Spieth J, Stage DE, Stark A, Stephan W, Strausberg RL, Strempel S, Sturgill D, Sutton G, Sutton GG, Tao W, Teichmann S, Tobari YN, Tomimura Y, Tsolas JM, Valente VL, Venter E, Venter JC, Vicario S, Vieira FG, Vilella AJ, Villasante A, Walenz B, Wang J, Wasserman M, Watts T, Wilson D, Wilson RK, Wing RA, Wolfner MF, Wong A, Wong GK, Wu CI, Wu G, Yamamoto D, Yang HP, Yang SP, Yorke JA, Yoshida K, Zdobnov E, Zhang P, Zhang Y, Zimin AV, Baldwin J, Abdouelleil A, Abdulkadir J, Abebe A, Abera B, Abreu J, Acer SC, Aftuck L, Alexander A, An P, Anderson E, Anderson S, Arachi H, Azer M, Bachantsang P, Barry A, Bayul T, Berlin A, Bessette D, Bloom T, Blye J, Boguslavskiy L, Bonnet C, Boukhgalter B, Bourzgui I, Brown A, Cahill P, Channer S, Cheshatsang Y, Chuda L, Citroen M, Collymore A, Cooke P, Costello M, D'Aco K, Daza R, De Haan G, DeGray S, DeMaso C, Dhargay N, Dooley K, Dooley E, Doricent M, Dorje P, Dorjee K, Dupes A, Elong R, Falk J, Farina A, Faro S, Ferguson D, Fisher S, Foley CD, Franke A, Friedrich D, Gadbois L, Gearin G, Gearin CR, Giannoukos G, Goode T, Graham J, Grandbois E, Grewal S, Gyaltsen K, Hafez N, Hagos B, Hall J, Henson C, Hollinger A, Honan T, Huard MD, Hughes L, Hurhula B, Husby ME, Kamat A, Kanga B, Kashin S, Khazanovich D, Kisner P, Lance K, Lara M, Lee W, Lennon N, Letendre F, LeVine R, Lipovsky A, Liu X, Liu J, Liu S, Lokyitsang T, Lokyitsang Y, Lubonja R, Lui A, Macdonald P, Magnisalis V, Maru K, Matthews C, McCusker W, McDonough S, Mehta T, Meldrim J, Meneus L, Mihai O, Mihalev A, Mihova T, Mittelman R, Mlenga V, Montmayeur A, Mulrain L, Navidi A, Naylor J, Negash T, Nguyen T, Nguyen N, Nicol R, Norbu C, Norbu N, Novod N, O'Neill B, Osman S, Markiewicz E, Oyono OL, Patti C, Phunkhang P, Pierre F, Priest M, Raghuraman S, Rege F, Reyes R, Rise C, Rogov P, Ross K, Ryan E, Settipalli S, Shea T, Sherpa N, Shi L, Shih D, Sparrow T, Spaulding J, Stalker J, Stange-Thomann N, Stavropoulos S, Stone C, Strader C, Tesfaye S, Thomson T, Thoulutsang Y, Thoulutsang D, Topham K, Topping I, Tsamla T, Vassiliev H, Vo A, Wangchuk T, Wangdi T, Weiand M, Wilkinson J, Wilson A, Yadav S, Young G, Yu Q, Zembek L, Zhong D, Zimmer A, Zwirko Z, Alvarez P, Brockman W, Butler J, Chin C, Grabherr M, Kleber M, Mauceli E, MacCallum I (- 405) Ref: Nature, 450:203, 2007 : PubMed ESTHER: Clark_2007_Nature_450_203 PubMedSearch: Clark 2007 Nature 450 203 PubMedID: 17994087 Gene_locus related to this paper: droan-ACHE, droan-b3lx10, droan-b3lx75, droan-b3lxv7, droan-b3ly87, droan-b3lyh4, droan-b3lyh5, droan-b3lyh7, droan-b3lyh9, droan-b3lyi0, droan-b3lyi2, droan-b3lyi3, droan-b3lyi4, droan-b3lyj8, droan-b3lyj9, droan-b3lyx4, droan-b3lyx5, droan-b3lyx6, droan-b3lyx7, droan-b3lyx9, droan-b3lz72, droan-b3m1x3, droan-b3m2d4, droan-b3m3d9, droan-b3m4e3, droan-b3m5w1, droan-b3m6i7, droan-b3m7v2, droan-b3m9a5, droan-b3m9f4, droan-b3m9p3, droan-b3m254, droan-b3m259, droan-b3m260, droan-b3m262, droan-b3m524, droan-b3m635, droan-b3m845, droan-b3m846, droan-b3md01, droan-b3mdh7, droan-b3mdm6, droan-b3mdw8, droan-b3mee1, droan-b3mf47, droan-b3mf48, droan-b3mg94, droan-b3mgk2, droan-b3mgn6, droan-b3mii3, droan-b3mjk2, droan-b3mjk3, droan-b3mjk4, droan-b3mjk5, droan-b3mjl2, droan-b3mjl4, droan-b3mjl7, droan-b3mjl9, droan-b3mjm8, droan-b3mjm9, droan-b3mjs6, droan-b3mkr0, droan-b3ml20, droan-b3mly4, droan-b3mly5, droan-b3mly6, droan-b3mmm8, droan-b3mnb5, droan-b3mny9, droan-b3mtj5, droan-b3muw4, droan-b3muw8, droan-b3n0e7, droan-b3n2j7, droan-b3n247, droan-c5idb2, droer-ACHE, droer-b3n5c7, droer-b3n5d0, droer-b3n5d8, droer-b3n5d9, droer-b3n5t7, droer-b3n5y4, droer-b3n7d2, droer-b3n7d3, droer-b3n7d4, droer-b3n7k8, droer-b3n8e4, droer-b3n8f7, droer-b3n8f8, droer-b3n9e1, droer-b3n319, droer-b3n547, droer-b3n549, droer-b3n558, droer-b3n560, droer-b3n577, droer-b3n612, droer-b3nar5, droer-b3nb91, droer-b3nct9, droer-b3nd53, droer-b3ndh9, droer-b3ndq8, droer-b3ne66, droer-b3ne67, droer-b3ne97, droer-b3nfk3, droer-b3nfq9, droer-b3nim7, droer-b3nkn2, droer-b3nm11, droer-b3nmh4, droer-b3nmy2, droer-b3npx2, droer-b3npx3, droer-b3nq76, droer-b3nqg9, droer-b3nqm8, droer-b3nr28, droer-b3nrd3, droer-b3nst4, droer-b3nwa7, droer-b3nyp5.1, droer-b3nyp5.2, droer-b3nyp6, droer-b3nyp7, droer-b3nyp8, droer-b3nyp9, droer-b3nyq3, droer-b3nz06, droer-b3nz14, droer-b3nzj0, droer-b3p0c0, droer-b3p0c1, droer-b3p0c2, droer-b3p2x6, droer-b3p2x7, droer-b3p2x9, droer-b3p2y1, droer-b3p2y2, droer-b3p6d4, droer-b3p6d5, droer-b3p6w3, droer-b3p7b4, droer-b3p7h9, droer-b3p152, droer-b3p486, droer-b3p487, droer-b3p488, droer-b3p489, droer-EST6, droer-q670j5, drogr-ACHE, drogr-b4iwp3, drogr-b4iww3, drogr-b4iwy3, drogr-b4ixf7, drogr-b4ixh4, drogr-b4iyz5, drogr-b4j2s2, drogr-b4j2u8, drogr-b4j3u1, drogr-b4j3v3, drogr-b4j4g7, drogr-b4j4x9, drogr-b4j6e6, drogr-b4j9c9, drogr-b4j9y4, drogr-b4j156, drogr-b4j384, drogr-b4j605, drogr-b4j685, drogr-b4ja76, drogr-b4jay5, drogr-b4jcf0, drogr-b4jcf1, drogr-b4jdg6, drogr-b4jdg7, drogr-b4jdh6, drogr-b4jdz1, drogr-b4jdz2, drogr-b4jdz4, drogr-b4je66, drogr-b4je79, drogr-b4je82, drogr-b4je88, drogr-b4je89, drogr-b4je90, drogr-b4je91, drogr-b4jf76, drogr-b4jf79, drogr-b4jf80, drogr-b4jf81, drogr-b4jf82, drogr-b4jf83, drogr-b4jf84, drogr-b4jf85, drogr-b4jf87, drogr-b4jf91, drogr-b4jf92, drogr-b4jg66, drogr-b4jgh0, drogr-b4jgh1, drogr-b4jgr9, drogr-b4ji67, drogr-b4jls2, drogr-b4jnh9, drogr-b4jpc6, drogr-b4jpq3, drogr-b4jpx9, drogr-b4jql2, drogr-b4jrh5, drogr-b4jsb2, drogr-b4jth3, drogr-b4jti1, drogr-b4jul5, drogr-b4jur4, drogr-b4jvh3, drogr-b4jz00, drogr-b4jz03, drogr-b4jz04, drogr-b4jz05, drogr-b4jzh2, drogr-b4k0u2, drogr-b4k2r1, drogr-b4k234, drogr-b4k235, drome-BEM46, drome-CG3734, drome-CG9953, drome-CG11626, drome-GH02439, dromo-ACHE, dromo-b4k6a7, dromo-b4k6a8, dromo-b4k6q8, dromo-b4k6q9, dromo-b4k6r1, dromo-b4k6r3, dromo-b4k6r4, dromo-b4k6r5, dromo-b4k6r6, dromo-b4k6r7, dromo-b4k6r8, dromo-b4k6r9, dromo-b4k6s0, dromo-b4k6s1, dromo-b4k6s2, dromo-b4k9c7, dromo-b4k9d3, dromo-b4k571, dromo-b4k721, dromo-b4ka74, dromo-b4ka89, dromo-b4kaj4, dromo-b4kc20, dromo-b4kcl2, dromo-b4kcl3, dromo-b4kd55.1, dromo-b4kd55.2, dromo-b4kd56, dromo-b4kd57, dromo-b4kde1, dromo-b4kdg2, dromo-b4kdh4, dromo-b4kdh5, dromo-b4kdh6, dromo-A0A0Q9XDF2, dromo-b4kdh8.1, dromo-b4kdh8.2, dromo-b4kg04, dromo-b4kg05, dromo-b4kg06, dromo-b4kg16, dromo-b4kg44, dromo-b4kg90, dromo-b4kh20, dromo-b4kh21, dromo-b4kht7, dromo-b4kid3, dromo-b4kik0, dromo-b4kjx0, dromo-b4kki1, dromo-b4kkp6, dromo-b4kkp8, dromo-b4kkq8, dromo-b4kkr0, dromo-b4kkr3, dromo-b4kkr4, dromo-b4kks0, dromo-b4kks1, dromo-b4kks2, dromo-b4kla1, dromo-b4klv8, dromo-b4knt4, dromo-b4kp08, dromo-b4kp16, dromo-b4kqa6, dromo-b4kqa7, dromo-b4kqa8, dromo-b4kqh1, dromo-b4kst4, dromo-b4ksy6, dromo-b4kt84, dromo-b4ktf5, dromo-b4ktf6, dromo-b4kvl3, dromo-b4kvw2, dromo-b4kwv4, dromo-b4kwv5, dromo-b4kxz6, dromo-b4ky12, dromo-b4ky36, dromo-b4ky44, dromo-b4kzu7, dromo-b4l0n8, dromo-b4l4u5, dromo-b4l6l9, dromo-b4l084, drope-ACHE, drope-b4g3s6, drope-b4g4p7, drope-b4g6v4, drope-b4g8m0, drope-b4g8n6, drope-b4g8n7, drope-b4g9p2, drope-b4g815, drope-b4g816, drope-b4gat7, drope-b4gav5, drope-b4gb05, drope-b4gc08, drope-b4gcr3, drope-b4gdk2, drope-b4gdl9, drope-b4gdv9, drope-b4gei8, drope-b4gei9, drope-b4gej0, drope-b4ghz9, drope-b4gj62, drope-b4gj64, drope-b4gj74, drope-b4gkf4, drope-b4gkv2, drope-b4gky9, drope-b4gl76, drope-b4glf3, drope-b4gmt3, drope-b4gmt7, drope-b4gmt9, drope-b4gmu2, drope-b4gmu3, drope-b4gmu4, drope-b4gmu5, drope-b4gmu6, drope-b4gmu7, drope-b4gmv1, drope-b4gn08, drope-b4gpa7, drope-b4gq13, drope-b4grh7, drope-b4gsf9, drope-b4gsw4, drope-b4gsw5, drope-b4gsx2, drope-b4gsx7, drope-b4gsy6, drope-b4gsy7, drope-b4guj8, drope-b4gw36, drope-b4gzc2, drope-b4gzc6, drope-b4gzc7, drope-b4h4p9, drope-b4h5l3, drope-b4h6a0, drope-b4h6a8, drope-b4h6a9, drope-b4h6b0, drope-b4h7m7, drope-b4h462, drope-b4h601, drope-b4h602, drope-b4hay1, drope-b4hb18, drope-est5a, drope-est5b, drope-est5c, drops-ACHE, drops-b5dhd2, drops-b5dk96, drops-b5dpe3, drops-b5drp9, drops-b5dwa7, drops-b5dwa8, drops-b5dz85, drops-b5dz86, drops-est5a, drops-est5b, drops-q29bq2, drops-q29dd7, drops-q29ew0, drops-q291d5, drops-q291e8, drops-q293n1, drops-q293n4, drops-q293n5, drops-q293n6, drops-q294n6, drops-q294n7, drops-q294n9, drops-q294p4, drose-b4he97, drose-b4hfu2, drose-b4hg54, drose-b4hga0, drose-b4hgu9, drose-b4hgv0, drose-b4hgv3, drose-b4hgv4, drose-b4hhm8, drose-b4hhs6, drose-b4hie4, drose-b4him9, drose-b4hk63, drose-b4hkj5, drose-b4hr07, drose-b4hr81, drose-b4hre7, drose-b4hs13, drose-b4hsj9, drose-b4hsk0, drose-b4hsm8, drose-b4hvr5, drose-b4hwr7, drose-b4hwr8, drose-b4hwr9, drose-b4hws6, drose-b4hws7, drose-b4hwt0, drose-b4hwt2, drose-b4hwu1, drose-b4hwu2, drose-b4hxs9, drose-b4hxu4, drose-b4hxz1, drose-b4hyp8, drose-b4hyp9, drose-b4hyq0, drose-b4hyz4, drose-b4hyz5, drose-b4i1k8, drose-b4i2f3, drose-b4i2w5, drose-b4i4u3, drose-b4i4u7, drose-b4i4u9, drose-b4i4v0, drose-b4i4v1, drose-b4i4v4, drose-b4i4v5, drose-b4i4v6, drose-b4i4v7, drose-b4i4v8, drose-b4i4w0, drose-b4i7s6, drose-b4i133, drose-b4i857, drose-b4iam7, drose-b4iam9, drose-b4iaq6, drose-b4icf6, drose-b4icf7, drose-b4id80, drose-b4ifc5, drose-b4ihv9, drose-b4iie9, drose-b4ilj8, drose-b4in13, drose-b4inj9, drosi-ACHE, drosi-aes04a, drosi-b4nsh8, drosi-b4q3d7, drosi-b4q4w5, drosi-b4q4y7, drosi-b4q6h6, drosi-b4q7u2, drosi-b4q7u3, drosi-b4q9c6, drosi-b4q9c7, drosi-b4q9d3, drosi-b4q9d4, drosi-b4q9r0, drosi-b4q9r1, drosi-b4q9r3, drosi-b4q9s2, drosi-b4q9s3, drosi-b4q429, drosi-b4q530, drosi-b4q734, drosi-b4q782, drosi-b4q783, drosi-b4q942, drosi-b4qet1, drosi-b4qfv6, drosi-b4qge5, drosi-b4qgh5, drosi-b4qgs5, drosi-b4qhf3, drosi-b4qhf4, drosi-b4qhi5, drosi-b4qjr2, drosi-b4qjr3, drosi-b4qjv6, drosi-b4qk23, drosi-b4qk51, drosi-b4qlt1, drosi-b4qlz9, drosi-b4qmn9, drosi-b4qrq7, drosi-b4qs01, drosi-b4qs57, drosi-b4qs82, drosi-b4qs83, drosi-b4qs84, drosi-b4qs85, drosi-b4qs86, drosi-b4qsq1, drosi-b4quk6, drosi-b4qvg5, drosi-b4qvg6, drosi-b4qzn2, drosi-b4qzn3, drosi-b4qzn5, drosi-b4qzn7, drosi-b4qzn8, drosi-b4qzp2, drosi-b4qzp3, drosi-b4qzp4, drosi-b4qzp5, drosi-b4qzp6, drosi-b4qzp7, drosi-b4r1a4, drosi-b4r025, drosi-b4r207, drosi-b4r662, drosi-este6, drosi-q670k8, drovi-ACHE, drovi-b4lev2, drovi-b4lf33, drovi-b4lf51, drovi-b4lg54, drovi-b4lg72, drovi-b4lgc6, drovi-b4lgd5, drovi-b4lgg0, drovi-b4lgk5, drovi-b4lgn2, drovi-b4lh17, drovi-b4lh18, drovi-b4lk43, drovi-b4ll59, drovi-b4ll60, drovi-b4llm5, drovi-b4lln3, drovi-b4lmk4, drovi-b4lmp0, drovi-b4lnr4, drovi-b4lp47, drovi-b4lpd0, drovi-b4lps0, drovi-b4lqc6, drovi-b4lr00, drovi-b4lrp6, drovi-b4lrw2, drovi-b4lse7, drovi-b4lse9, drovi-b4lsf0, drovi-b4lsn0, drovi-b4lsq5, drovi-b4lt32, drovi-b4ltr1, drovi-b4lui7, drovi-b4lui9, drovi-b4luj8, drovi-b4luk0, drovi-b4luk3, drovi-b4luk8, drovi-b4luk9, drovi-b4lul0, drovi-b4lve2, drovi-b4lxi9, drovi-b4lxj8, drovi-b4lyf3, drovi-b4lyq2, drovi-b4lyq3, drovi-b4lz07, drovi-b4lz13, drovi-b4lz14, drovi-b4lz15, drovi-b4m0j7, drovi-b4m0s0, drovi-b4m2b6, drovi-b4m4h7, drovi-b4m4h8, drovi-b4m4i0, drovi-b4m4i2, drovi-b4m4i3.A, drovi-b4m4i3.B, drovi-b4m4i4, drovi-b4m4i5, drovi-b4m4i6, drovi-b4m4i7, drovi-b4m4i8, drovi-b4m4i9, drovi-b4m4j2, drovi-b4m5a0, drovi-b4m5a1, drovi-b4m5a2, drovi-b4m6b9, drovi-b4m7k9, drovi-b4m9g9, drovi-b4m9h0, drovi-b4m564, drovi-b4m599, drovi-b4m918, drovi-b4mb87, drovi-b4mc71, drovi-b4mfa4, drowi-ACHE, drowi-b4mjb9, drowi-b4mkt7, drowi-b4mlc1, drowi-b4mp68, drowi-b4mqe9, drowi-b4mqf0.2, drowi-b4mqf1, drowi-b4mqf3, drowi-b4mqf4, drowi-b4mqf5, drowi-b4mqq6, drowi-b4mrd1, drowi-b4mrk3, drowi-b4mtl5, drowi-b4mug2, drowi-b4muj8, drowi-b4mv18, drowi-b4mw32, drowi-b4mw85, drowi-b4mwp2, drowi-b4mwp6, drowi-b4mwq5, drowi-b4mwr0, drowi-b4mwr8, drowi-b4mwr9, drowi-b4mwt1, drowi-b4mwz7, drowi-b4mxn5, drowi-b4my54, drowi-b4myg1, drowi-b4myh5, drowi-b4n0d4, drowi-b4n1a7, drowi-b4n1c8, drowi-b4n3s9, drowi-b4n3x7, drowi-b4n4x9, drowi-b4n4y0, drowi-b4n6m1, drowi-b4n6n0, drowi-b4n6n7, drowi-b4n6u6, drowi-b4n7s6, drowi-b4n7s7, drowi-b4n7s8, drowi-b4n899.1, drowi-b4n8a1, drowi-b4n8a2, drowi-b4n8a3, drowi-b4n8a4, drowi-b4n8a9, drowi-b4n023, drowi-b4n075, drowi-b4n543, drowi-b4n888, drowi-b4n889, drowi-b4n891, drowi-b4n893, drowi-b4n895, drowi-b4n897, drowi-b4n898, drowi-b4n899.2, drowi-b4nae3, drowi-b4ner8, drowi-b4ng76, drowi-b4nga7, drowi-b4ngb5, drowi-b4nhz9, drowi-b4nj18, drowi-b4nj19, drowi-b4nja7, drowi-b4nja8, drowi-b4nja9, drowi-b4njk8, drowi-b4nkc8, drowi-b4nky0, drowi-b4nl36, drowi-b4nm27, drowi-b4nn59, drowi-b4nnc1, drowi-b4nng1, drowi-b4nng2, droya-ACHE, droya-aes04, droya-b4itg2, droya-b4itg6, droya-b4itu9, droya-b4iuv4, droya-b4iuv5, droya-b4nxe6, droya-b4nxg5, droya-b4nxg6, droya-b4nxg8, droya-b4nxw4, droya-b4ny57, droya-b4ny58, droya-b4ny86, droya-b4nzz8, droya-b4p0b5, droya-b4p0q9, droya-b4p0r0, droya-b4p0r7, droya-b4p0r8, droya-b4p0r9, droya-b4p0s0, droya-b4p0s2, droya-b4p0t0, droya-b4p0t1, droya-b4p3h4, droya-b4p3x8, droya-b4p5g8, droya-b4p6c9, droya-b4p6l9, droya-b4p6r1, droya-b4p6r2, droya-b4p7u4, droya-b4p8w7, droya-b4p023, droya-b4p241, droya-b4p774, droya-b4pat9, droya-b4pbl1, droya-b4pd22, droya-b4pd70, droya-b4pdm8, droya-b4pet9, droya-b4pff9, droya-b4pga7, droya-b4pgu0, droya-b4pig3, droya-b4pjt8, droya-b4pka2, droya-b4plh2, droya-b4pma3, droya-b4pmv3, droya-b4pmv4, droya-b4pmv5, droya-b4pn92, droya-b4pp65, droya-b4ppc5, droya-b4ppc6, droya-b4ppc7, droya-b4ppc8, droya-b4pq03, droya-b4prg6B, droya-b4prg9, droya-b4prh3, droya-b4prh4, droya-b4prh6, droya-b4prh7, droya-b4psz8, droya-b4psz9, droya-b4pv22, droya-b4q0g5, droya-b4q246, droya-EST6, droya-q71d76, drowi-b4n7m9, drope-b4gkk1, droer-b3n5s3, drose-b4i1w5, drowi-a0a0q9x0t3, drogr-b4jvm7, dromo-b4ku70, drovi-b4mcn9, drovi-b4lty2, drogr-b4jdu1, drovi-a0a0q9wiq8, dromo-b4kf70, drosi-b2zi86, droya-b4p2y4, drose-b2zic5, droer-b3n895 Abstract Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species. Title: Characterization of a marine gammaproteobacterium capable of aerobic anoxygenic photosynthesis Fuchs BM, Spring S, Teeling H, Quast C, Wulf J, Schattenhofer M, Yan S, Ferriera S, Johnson J and Amann R <1 more author(s)> Fuchs BM, Spring S, Teeling H, Quast C, Wulf J, Schattenhofer M, Yan S, Ferriera S, Johnson J, Glockner FO, Amann R (- 1) Ref: Proc Natl Acad Sci U S A, 104:2891, 2007 : PubMed ESTHER: Fuchs_2007_Proc.Natl.Acad.Sci.U.S.A_104_2891 PubMedSearch: Fuchs 2007 Proc.Natl.Acad.Sci.U.S.A 104 2891 PubMedID: 17299055 Gene_locus related to this paper: 9gamm-a4a7a9, 9gamm-a4a9u6, 9gamm-a4a440, 9gamm-a4a484, 9gamm-a4a590, 9gamm-a4a746, 9gamm-a4a758, 9gamm-a4aa23, 9gamm-a4acc1, 9gamm-a4ada0, 9gamm-a4ae00, 9gamm-a4acf4, 9gamm-a4acr9 Abstract Members of the gammaproteobacterial clade NOR5/OM60 regularly form an abundant part, up to 11%, of the bacterioplankton community in coastal systems during the summer months. Here, we report the nearly complete genome sequence of one cultured representative, Congregibacter litoralis strain KT71, isolated from North Sea surface water. Unexpectedly, a complete photosynthesis superoperon, including genes for accessory pigments, was discovered. It has a high sequence similarity to BAC clones from Monterey Bay [Beja O, Suzuki MT, Heidelberg JF, Nelson WC, Preston CM, et al. (2002) Nature 415:630-633], which also share a nearly identical gene arrangement. Although cultures of KT71 show no obvious pigmentation, bacteriochlorophyll a and spirilloxanthin-like carotenoids could be detected by HPLC analysis in cell extracts. The presence of two potential BLUF (blue light using flavin adenine dinucleotide sensors), one of which was found adjacent to the photosynthesis operon in the genome, indicates a light- and redox-dependent regulation of gene expression. Like other aerobic anoxygenic phototrophs (AAnPs), KT71 is able to grow neither anaerobically nor photoautotrophically. Cultivation experiments and genomic evidence show that KT71 needs organic substrates like carboxylic acids, oligopeptides, or fatty acids for growth. The strain grows optimally under microaerobic conditions and actively places itself in a zone of approximately 10% oxygen saturation. The genome analysis of C. litoralis strain KT71 identifies the gammaproteobacterial marine AAnPs, postulated based on BAC sequences, as members of the NOR5/OM60 clade. KT71 enables future experiments investigating the importance of this group of gammaproteobacterial AAnPs in coastal environments. Title: Effect of initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and metformin on glycemic control in patients with type 2 diabetes Goldstein BJ, Feinglos MN, Lunceford JK, Johnson J, Williams-Herman DE Ref: Diabetes Care, 30:1979, 2007 : PubMed ESTHER: Goldstein_2007_Diabetes.Care_30_1979 PubMedSearch: Goldstein 2007 Diabetes.Care 30 1979 PubMedID: 17485570 Abstract OBJECTIVE: To assess the efficacy and safety of initial combination therapy with sitagliptin and metformin in patients with type 2 diabetes and inadequate glycemic control on diet and exercise. RESEARCH DESIGN AND METHODS: In a 24-week, randomized, double-blind, placebo-controlled, parallel-group study, 1,091 patients with type 2 diabetes and A1C 7.5-11% were randomized to one of six daily treatments: sitagliptin 100 mg/metformin 1,000 mg (S100/M1000 group), sitagliptin 100 mg/metformin 2,000 mg (S100/M2000 group), metformin 1,000 mg (M1000 group), metformin 2,000 mg (M2000 group) (all as divided doses administered twice daily [b.i.d.]), sitagliptin 100 mg q.d. (S100 group), or placebo. Patients who had an A1C >11% or a fasting glucose value >280 mg/dl after the run-in period were not eligible to be randomized; these patients could participate in an open-label substudy and were treated with S100/M2000 for 24 weeks. RESULTS: The mean baseline A1C was 8.8% in the randomized patients. The placebo-subtracted A1C change from baseline was -2.07% (S100/M2000), -1.57% (S100/M1000), -1.30% (M2000), -0.99% (M1000), and -0.83% (S100) (P < 0.001 for comparisons versus placebo and for coadministration versus respective monotherapies). The proportion of patients achieving an A1C <7% and <6.5% was 66 and 44%, respectively, in the S100/M2000 group (P < 0.001 vs. S100 or M2000). For the open-label cohort (n = 117; baseline A1C 11.2%) treated with S100/M2000, the within-group mean A1C change from baseline was -2.9%. The incidence of hypoglycemia was low (0.5-2.2%) across active treatment groups and not significantly different from that in the placebo group (0.6%). The incidence of gastrointestinal adverse experiences was similar for coadministration therapies compared with their respective metformin monotherapy. CONCLUSIONS: The initial combination of sitagliptin and metformin provided substantial and additive glycemic improvement and was generally well tolerated in patients with type 2 diabetes. Title: Patterns and implications of gene gain and loss in the evolution of Prochlorococcus Kettler GC, Martiny AC, Huang K, Zucker J, Coleman ML, Rodrigue S, Chen F, Lapidus A, Ferriera S and Chisholm SW <4 more author(s)> Kettler GC, Martiny AC, Huang K, Zucker J, Coleman ML, Rodrigue S, Chen F, Lapidus A, Ferriera S, Johnson J, Steglich C, Church GM, Richardson P, Chisholm SW (- 4) Ref: PLoS Genet, 3:e231, 2007 : PubMed ESTHER: Kettler_2007_PLoS.Genet_3_e231 PubMedSearch: Kettler 2007 PLoS.Genet 3 e231 PubMedID: 18159947 Gene_locus related to this paper: prom1-a2c3n7, prom1-a2c150, prom1-a2c179, prom2-a8g5b6, prom2-a8g5t3, prom3-a2c804, prom3-a2cas9, prom4-a9b9z4, prom4-a9bb64, prom4-a9bbd7, prom5-a2bvt3, prom5-a2bx34, prom9-q31br4, prom9-q31ch4, promr-b9p0y6, promm-q7v6l0, promm-q7v8g2, proms-a2brm5, proms-a2bs42, promt-q46jt5, promt-q46jy1, promt-q46kg4, prom0-a3pbw6, proms-a2bq73, prom3-a2cay5, prom5-a2buz4, prom2-a8g328, prom3-a2ce38 Abstract Prochlorococcus is a marine cyanobacterium that numerically dominates the mid-latitude oceans and is the smallest known oxygenic phototroph. Numerous isolates from diverse areas of the world's oceans have been studied and shown to be physiologically and genetically distinct. All isolates described thus far can be assigned to either a tightly clustered high-light (HL)-adapted clade, or a more divergent low-light (LL)-adapted group. The 16S rRNA sequences of the entire Prochlorococcus group differ by at most 3%, and the four initially published genomes revealed patterns of genetic differentiation that help explain physiological differences among the isolates. Here we describe the genomes of eight newly sequenced isolates and combine them with the first four genomes for a comprehensive analysis of the core (shared by all isolates) and flexible genes of the Prochlorococcus group, and the patterns of loss and gain of the flexible genes over the course of evolution. There are 1,273 genes that represent the core shared by all 12 genomes. They are apparently sufficient, according to metabolic reconstruction, to encode a functional cell. We describe a phylogeny for all 12 isolates by subjecting their complete proteomes to three different phylogenetic analyses. For each non-core gene, we used a maximum parsimony method to estimate which ancestor likely first acquired or lost each gene. Many of the genetic differences among isolates, especially for genes involved in outer membrane synthesis and nutrient transport, are found within the same clade. Nevertheless, we identified some genes defining HL and LL ecotypes, and clades within these broad ecotypes, helping to demonstrate the basis of HL and LL adaptations in Prochlorococcus. Furthermore, our estimates of gene gain events allow us to identify highly variable genomic islands that are not apparent through simple pairwise comparisons. These results emphasize the functional roles, especially those connected to outer membrane synthesis and transport that dominate the flexible genome and set it apart from the core. Besides identifying islands and demonstrating their role throughout the history of Prochlorococcus, reconstruction of past gene gains and losses shows that much of the variability exists at the "leaves of the tree," between the most closely related strains. Finally, the identification of core and flexible genes from this 12-genome comparison is largely consistent with the relative frequency of Prochlorococcus genes found in global ocean metagenomic databases, further closing the gap between our understanding of these organisms in the lab and the wild. Title: Survey sequencing and comparative analysis of the elephant shark (Callorhinchus milii) genome Venkatesh B, Kirkness EF, Loh YH, Halpern AL, Lee AP, Johnson J, Dandona N, Viswanathan LD, Tay A and Brenner S <2 more author(s)> Venkatesh B, Kirkness EF, Loh YH, Halpern AL, Lee AP, Johnson J, Dandona N, Viswanathan LD, Tay A, Venter JC, Strausberg RL, Brenner S (- 2) Ref: PLoS Biol, 5:e101, 2007 : PubMed ESTHER: Venkatesh_2007_PLoS.Biol_5_E101 PubMedSearch: Venkatesh 2007 PLoS.Biol 5 E101 PubMedID: 17407382 Gene_locus related to this paper: calmi-a0a4w3h3v0, calmi-a0a4w3hel5 Abstract Owing to their phylogenetic position, cartilaginous fishes (sharks, rays, skates, and chimaeras) provide a critical reference for our understanding of vertebrate genome evolution. The relatively small genome of the elephant shark, Callorhinchus milii, a chimaera, makes it an attractive model cartilaginous fish genome for whole-genome sequencing and comparative analysis. Here, the authors describe survey sequencing (1.4x coverage) and comparative analysis of the elephant shark genome, one of the first cartilaginous fish genomes to be sequenced to this depth. Repetitive sequences, represented mainly by a novel family of short interspersed element-like and long interspersed element-like sequences, account for about 28% of the elephant shark genome. Fragments of approximately 15,000 elephant shark genes reveal specific examples of genes that have been lost differentially during the evolution of tetrapod and teleost fish lineages. Interestingly, the degree of conserved synteny and conserved sequences between the human and elephant shark genomes are higher than that between human and teleost fish genomes. Elephant shark contains putative four Hox clusters indicating that, unlike teleost fish genomes, the elephant shark genome has not experienced an additional whole-genome duplication. These findings underscore the importance of the elephant shark as a critical reference vertebrate genome for comparative analysis of the human and other vertebrate genomes. This study also demonstrates that a survey-sequencing approach can be applied productively for comparative analysis of distantly related vertebrate genomes. Title: Ancient noncoding elements conserved in the human genome Venkatesh B, Kirkness EF, Loh YH, Halpern AL, Lee AP, Johnson J, Dandona N, Viswanathan LD, Tay A and Brenner S <2 more author(s)> Venkatesh B, Kirkness EF, Loh YH, Halpern AL, Lee AP, Johnson J, Dandona N, Viswanathan LD, Tay A, Venter JC, Strausberg RL, Brenner S (- 2) Ref: Science, 314:1892, 2006 : PubMed ESTHER: Venkatesh_2006_Science_314_1892 PubMedSearch: Venkatesh 2006 Science 314 1892 PubMedID: 17185593 Gene_locus related to this paper: calmi-a0a4w3h3v0, calmi-a0a4w3hel5 Abstract Cartilaginous fishes represent the living group of jawed vertebrates that diverged from the common ancestor of human and teleost fish lineages about 530 million years ago. We generated approximately 1.4x genome sequence coverage for a cartilaginous fish, the elephant shark (Callorhinchus milii), and compared this genome with the human genome to identify conserved noncoding elements (CNEs). The elephant shark sequence revealed twice as many CNEs as were identified by whole-genome comparisons between teleost fishes and human. The ancient vertebrate-specific CNEs in the elephant shark and human genomes are likely to play key regulatory roles in vertebrate gene expression. Title: The genome of the African trypanosome Trypanosoma brucei Berriman M, Ghedin E, Hertz-Fowler C, Blandin G, Renauld H, Bartholomeu DC, Lennard NJ, Caler E, Hamlin NE and El-Sayed NM <92 more author(s)> Berriman M, Ghedin E, Hertz-Fowler C, Blandin G, Renauld H, Bartholomeu DC, Lennard NJ, Caler E, Hamlin NE, Haas B, Bohme U, Hannick L, Aslett MA, Shallom J, Marcello L, Hou L, Wickstead B, Alsmark UC, Arrowsmith C, Atkin RJ, Barron AJ, Bringaud F, Brooks K, Carrington M, Cherevach I, Chillingworth TJ, Churcher C, Clark LN, Corton CH, Cronin A, Davies RM, Doggett J, Djikeng A, Feldblyum T, Field MC, Fraser A, Goodhead I, Hance Z, Harper D, Harris BR, Hauser H, Hostetler J, Ivens A, Jagels K, Johnson D, Johnson J, Jones K, Kerhornou AX, Koo H, Larke N, Landfear S, Larkin C, Leech V, Line A, Lord A, MacLeod A, Mooney PJ, Moule S, Martin DM, Morgan GW, Mungall K, Norbertczak H, Ormond D, Pai G, Peacock CS, Peterson J, Quail MA, Rabbinowitsch E, Rajandream MA, Reitter C, Salzberg SL, Sanders M, Schobel S, Sharp S, Simmonds M, Simpson AJ, Tallon L, Turner CM, Tait A, Tivey AR, Van Aken S, Walker D, Wanless D, Wang S, White B, White O, Whitehead S, Woodward J, Wortman J, Adams MD, Embley TM, Gull K, Ullu E, Barry JD, Fairlamb AH, Opperdoes F, Barrell BG, Donelson JE, Hall N, Fraser CM, Melville SE, El-Sayed NM (- 92) Ref: Science, 309:416, 2005 : PubMed ESTHER: Berriman_2005_Science_309_416 PubMedSearch: Berriman 2005 Science 309 416 PubMedID: 16020726 Gene_locus related to this paper: tryb2-q6h9e3, tryb2-q6ha27, tryb2-q38cd5, tryb2-q38cd6, tryb2-q38cd7, tryb2-q38dc1, tryb2-q38de4, tryb2-q38ds6, tryb2-q38dx1, tryb2-q380z6, tryb2-q382c1, tryb2-q382l4, tryb2-q383a9, tryb2-q386e3, tryb2-q387r7, tryb2-q388n1, tryb2-q389w3, trybr-PEPTB, trycr-q4cq28, trycr-q4cq94, trycr-q4cq95, trycr-q4cq96, trycr-q4csm0, trycr-q4cwv3, trycr-q4cx66, trycr-q4cxr6, trycr-q4cyc5, trycr-q4cyf6, trycr-q4d3a2, trycr-q4d3x3, trycr-q4d3y4, trycr-q4d6h1, trycr-q4d8h8, trycr-q4d8h9, trycr-q4d8i0, trycr-q4d786, trycr-q4d975, trycr-q4da08, trycr-q4dap6, trycr-q4dbm2, trycr-q4dbn1, trycr-q4ddw7, trycr-q4de42, trycr-q4dhn8, trycr-q4dkk8, trycr-q4dkk9, trycr-q4dm56, trycr-q4dqa6, trycr-q4dt91, trycr-q4dvp2, trycr-q4dw34, trycr-q4dwm3, trycr-q4dy49, trycr-q4dy82, trycr-q4dzp6, trycr-q4e3m8, trycr-q4e4t5, trycr-q4e5d1, trycr-q4e5z2 Abstract African trypanosomes cause human sleeping sickness and livestock trypanosomiasis in sub-Saharan Africa. We present the sequence and analysis of the 11 megabase-sized chromosomes of Trypanosoma brucei. The 26-megabase genome contains 9068 predicted genes, including approximately 900 pseudogenes and approximately 1700 T. brucei-specific genes. Large subtelomeric arrays contain an archive of 806 variant surface glycoprotein (VSG) genes used by the parasite to evade the mammalian immune system. Most VSG genes are pseudogenes, which may be used to generate expressed mosaic genes by ectopic recombination. Comparisons of the cytoskeleton and endocytic trafficking systems with those of humans and other eukaryotic organisms reveal major differences. A comparison of metabolic pathways encoded by the genomes of T. brucei, T. cruzi, and Leishmania major reveals the least overall metabolic capability in T. brucei and the greatest in L. major. Horizontal transfer of genes of bacterial origin has contributed to some of the metabolic differences in these parasites, and a number of novel potential drug targets have been identified. Title: The identification of vesicular glutamate transporter 3 suggests novel modes of signaling by glutamate Fremeau RT, Jr., Burman J, Qureshi T, Tran CH, Proctor J, Johnson J, Zhang H, Sulzer D, Copenhagen DR and Edwards RH <3 more author(s)> Fremeau RT, Jr., Burman J, Qureshi T, Tran CH, Proctor J, Johnson J, Zhang H, Sulzer D, Copenhagen DR, Storm-Mathisen J, Reimer RJ, Chaudhry FA, Edwards RH (- 3) Ref: Proc Natl Acad Sci U S A, 99:14488, 2002 : PubMed ESTHER: Fremeau_2002_Proc.Natl.Acad.Sci.U.S.A_99_14488 PubMedSearch: Fremeau 2002 Proc.Natl.Acad.Sci.U.S.A 99 14488 PubMedID: 12388773 Abstract Quantal release of the principal excitatory neurotransmitter glutamate requires a mechanism for its transport into secretory vesicles. Within the brain, the complementary expression of vesicular glutamate transporters (VGLUTs) 1 and 2 accounts for the release of glutamate by all known excitatory neurons. We now report the identification of VGLUT3 and its expression by many cells generally considered to release a classical transmitter with properties very different from glutamate. Remarkably, subpopulations of inhibitory neurons as well as cholinergic interneurons, monoamine neurons, and glia express VGLUT3. The dendritic expression of VGLUT3 by particular neurons also indicates the potential for retrograde synaptic signaling. The distribution and subcellular location of VGLUT3 thus suggest novel modes of signaling by glutamate. Title: The anterior/posterior polarity of somites is disrupted in paraxis-deficient mice Johnson J, Rhee J, Parsons SM, Brown D, Olson EN, Rawls A Ref: Developmental Biology, 229:176, 2001 : PubMed ESTHER: Johnson_2001_Dev.Biol_229_176 PubMedSearch: Johnson 2001 Dev.Biol 229 176 PubMedID: 11133162 Abstract Establishing the anterior/posterior (A/P) boundary of individual somites is important for setting up the segmental body plan of all vertebrates. Resegmentation of adjacent sclerotomes to form the vertebrae and selective migration of neural crest cells during the formation of the dorsal root ganglia and peripheral nerves occur in response to differential expression of genes in the anterior and posterior halves of the somite. Recent evidence indicates that the A/P axis is established at the anterior end of the presomitic mesoderm prior to overt somitogenesis in response to both Mesp2 and Notch signaling. Here, we report that mice deficient for paraxis, a gene required for somite epithelialization, also display defects in the axial skeleton and peripheral nerves that are consistent with a failure in A/P patterning. Expression of Mesp2 and genes in the Notch pathway were not altered in the presomitic mesoderm of paraxis(-/-) embryos. Furthermore, downstream targets of Notch activation in the presomitic mesoderm, including EphA4, were transcribed normally, indicating that paraxis was not required for Notch signaling. However, genes that were normally restricted to the posterior half of somites were present in a diffuse pattern in the paraxis(-/-) embryos, suggesting a loss of A/P polarity. Collectively, these data indicate a role for paraxis in maintaining somite polarity that is independent of Notch signaling. Title: Short, Strong Hydrogen Bonds at the Active Site of Human Acetylcholinesterase: Proton NMR Studies Massiah MA, Viragh C, Reddy PM, Kovach IM, Johnson J, Rosenberry TL, Mildvan AS Ref: Biochemistry, 40:5682, 2001 : PubMed ESTHER: Massiah_2001_Biochemistry_40_5682 PubMedSearch: Massiah 2001 Biochemistry 40 5682 PubMedID: 11341833 Abstract Cholinesterases use a Glu-His-Ser catalytic triad to enhance the nucleophilicity of the catalytic serine. We have previously shown by proton NMR that horse serum butyryl cholinesterase, like serine proteases, forms a short, strong hydrogen bond (SSHB) between the Glu-His pair upon binding mechanism-based inhibitors, which form tetrahedral adducts, analogous to the tetrahedral intermediates in catalysis [Viragh, C., et al. (2000) Biochemistry 39, 16200-16205]. We now extend these studies to human acetylcholinesterase, a 136 kDa homodimer. The free enzyme at pH 7.5 shows a proton resonance at 14.4 ppm assigned to an imidazole NH of the active-site histidine, but no deshielded proton resonances between 15 and 21 ppm. Addition of a 3-fold excess of the mechanism-based inhibitor m-(N,N,N-trimethylammonio)trifluoroacetophenone (TMTFA) induced the complete loss of the 14.4 ppm signal and the appearance of a broad, deshielded resonance of equal intensity with a chemical shift delta of 17.8 ppm and a D/H fractionation factor phi of 0.76 +/- 0.10, consistent with a SSHB between Glu and His of the catalytic triad. From an empirical correlation of delta with hydrogen bond lengths in small crystalline compounds, the length of this SSHB is 2.62 +/- 0.02 A, in agreement with the length of 2.63 +/- 0.03 A, independently obtained from phi. Upon addition of a 3-fold excess of the mechanism-based inhibitor 4-nitrophenyl diethyl phosphate (paraoxon) to the free enzyme at pH 7.5, and subsequent deethylation, two deshielded resonances of unequal intensity appeared at 16.6 and 15.5 ppm, consistent with SSHBs with lengths of 2.63 +/- 0.02 and 2.65 +/- 0.02 A, respectively, suggesting conformational heterogeneity of the active-site histidine as a hydrogen bond donor to either Glu-327 of the catalytic triad or to Glu-199, also in the active site. Conformational heterogeneity was confirmed with the methylphosphonate ester anion adduct of the active-site serine, which showed two deshielded resonances of equal intensity at 16.5 and 15.8 ppm with phi values of 0.47 +/- 0.10 and 0.49 +/- 0.10 corresponding to average hydrogen bond lengths of 2.59 +/- 0.04 and 2.61 +/- 0.04 A, respectively. Similarly, lowering the pH of the free enzyme to 5.1 to protonate the active-site histidine (pK(a) = 6.0 +/- 0.4) resulted in the appearance of two deshielded resonances, at 17.7 and 16.4 ppm, consistent with SSHBs with lengths of 2.62 +/- 0.02 and 2.63 +/- 0.02 A, respectively. The NMR-derived distances agree with those found in the X-ray structures of the homologous acetylcholinesterase from Torpedo californica complexed with TMTFA (2.66 +/- 0.28 A) and sarin (2.53 +/- 0.26 A) and at low pH (2.52 +/- 0.25 A). However, the order of magnitude greater precision of the NMR-derived distances establishes the presence of SSHBs at the active site of acetylcholinesterase, and detect conformational heterogeneity of the active-site histidine. We suggest that the high catalytic power of cholinesterases results in part from the formation of a SSHB between Glu and His of the catalytic triad. Title: The sequence of the human genome Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA and Zhu X <264 more author(s)> Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA, Holt RA, Gocayne JD, Amanatides P, Ballew RM, Huson DH, Wortman JR, Zhang Q, Kodira CD, Zheng XH, Chen L, Skupski M, Subramanian G, Thomas PD, Zhang J, Gabor Miklos GL, Nelson C, Broder S, Clark AG, Nadeau J, McKusick VA, Zinder N, Levine AJ, Roberts RJ, Simon M, Slayman C, Hunkapiller M, Bolanos R, Delcher A, Dew I, Fasulo D, Flanigan M, Florea L, Halpern A, Hannenhalli S, Kravitz S, Levy S, Mobarry C, Reinert K, Remington K, Abu-Threideh J, Beasley E, Biddick K, Bonazzi V, Brandon R, Cargill M, Chandramouliswaran I, Charlab R, Chaturvedi K, Deng Z, Di Francesco V, Dunn P, Eilbeck K, Evangelista C, Gabrielian AE, Gan W, Ge W, Gong F, Gu Z, Guan P, Heiman TJ, Higgins ME, Ji RR, Ke Z, Ketchum KA, Lai Z, Lei Y, Li Z, Li J, Liang Y, Lin X, Lu F, Merkulov GV, Milshina N, Moore HM, Naik AK, Narayan VA, Neelam B, Nusskern D, Rusch DB, Salzberg S, Shao W, Shue B, Sun J, Wang Z, Wang A, Wang X, Wang J, Wei M, Wides R, Xiao C, Yan C, Yao A, Ye J, Zhan M, Zhang W, Zhang H, Zhao Q, Zheng L, Zhong F, Zhong W, Zhu S, Zhao S, Gilbert D, Baumhueter S, Spier G, Carter C, Cravchik A, Woodage T, Ali F, An H, Awe A, Baldwin D, Baden H, Barnstead M, Barrow I, Beeson K, Busam D, Carver A, Center A, Cheng ML, Curry L, Danaher S, Davenport L, Desilets R, Dietz S, Dodson K, Doup L, Ferriera S, Garg N, Gluecksmann A, Hart B, Haynes J, Haynes C, Heiner C, Hladun S, Hostin D, Houck J, Howland T, Ibegwam C, Johnson J, Kalush F, Kline L, Koduru S, Love A, Mann F, May D, McCawley S, McIntosh T, McMullen I, Moy M, Moy L, Murphy B, Nelson K, Pfannkoch C, Pratts E, Puri V, Qureshi H, Reardon M, Rodriguez R, Rogers YH, Romblad D, Ruhfel B, Scott R, Sitter C, Smallwood M, Stewart E, Strong R, Suh E, Thomas R, Tint NN, Tse S, Vech C, Wang G, Wetter J, Williams S, Williams M, Windsor S, Winn-Deen E, Wolfe K, Zaveri J, Zaveri K, Abril JF, Guigo R, Campbell MJ, Sjolander KV, Karlak B, Kejariwal A, Mi H, Lazareva B, Hatton T, Narechania A, Diemer K, Muruganujan A, Guo N, Sato S, Bafna V, Istrail S, Lippert R, Schwartz R, Walenz B, Yooseph S, Allen D, Basu A, Baxendale J, Blick L, Caminha M, Carnes-Stine J, Caulk P, Chiang YH, Coyne M, Dahlke C, Mays A, Dombroski M, Donnelly M, Ely D, Esparham S, Fosler C, Gire H, Glanowski S, Glasser K, Glodek A, Gorokhov M, Graham K, Gropman B, Harris M, Heil J, Henderson S, Hoover J, Jennings D, Jordan C, Jordan J, Kasha J, Kagan L, Kraft C, Levitsky A, Lewis M, Liu X, Lopez J, Ma D, Majoros W, McDaniel J, Murphy S, Newman M, Nguyen T, Nguyen N, Nodell M, Pan S, Peck J, Peterson M, Rowe W, Sanders R, Scott J, Simpson M, Smith T, Sprague A, Stockwell T, Turner R, Venter E, Wang M, Wen M, Wu D, Wu M, Xia A, Zandieh A, Zhu X (- 264) Ref: Science, 291:1304, 2001 : PubMed ESTHER: Venter_2001_Science_291_1304 PubMedSearch: Venter 2001 Science 291 1304 PubMedID: 11181995 Gene_locus related to this paper: human-AADAC, human-ABHD1, human-ABHD10, human-ABHD11, human-ACHE, human-BCHE, human-LDAH, human-ABHD18, human-CMBL, human-ABHD17A, human-KANSL3, human-LIPA, human-LYPLAL1, human-NDRG2, human-NLGN3, human-NLGN4X, human-NLGN4Y, human-PAFAH2, human-PREPL, human-RBBP9, human-SPG21 Abstract A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies-a whole-genome assembly and a regional chromosome assembly-were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional approximately 12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge. Title: Blockade of glutamate- and cholinergic ion channels by amantadane derivatives Magazanik LG, Antonov SM, Lukomskaya NY, Potap'eva NN, Gmiro VE, Johnson J Ref: Neurosci Behav Physiol, 26:13, 1996 : PubMed ESTHER: Magazanik_1996_Neurosci.Behav.Physiol_26_13 PubMedSearch: Magazanik 1996 Neurosci.Behav.Physiol 26 13 PubMedID: 8801464 Title: Differential diagnosis of dementia, delirium and depression. Implications for drug therapy Johnson J, Sims R, Gottlieb G Ref: Drugs & Aging, 5:431, 1994 : PubMed ESTHER: Johnson_1994_Drugs.Aging_5_431 PubMedSearch: Johnson 1994 Drugs.Aging 5 431 PubMedID: 7858369 Abstract Dementia, delirium and depression are the 3 most prevalent mental disorders in the elderly. While dementia and depression are prevalent in the community, hospitals and nursing homes, delirium is seen most often in acute care hospitals. Much of the management of these syndromes is undertaken by primary care physicians rather than psychiatrists. Therefore, it is imperative that generalist physicians be adept at recognising, evaluating and managing patients with these syndromes. Because no diagnostic tests are pathognomonic of these syndromes, the differential diagnosis hinges on a careful clinical evaluation. The first step is to recognise which of the syndromes is present. Dementia is defined by a chronic loss of intellectual or cognitive function of sufficient severity to interfere with social or occupational function. Delirium is an acute disturbance of consciousness marked by an attention deficit and a change in cognitive function. Depression is an affective disorder evidenced by a dysphoric mood, but the most pervasive symptom is a loss of ability to enjoy usual activities. It is important to recognise that these syndromes are not mutually exclusive, as dementia frequently coexists with delirium and depression. Furthermore, physical diagnoses, such as chronic obstructive lung disease, congestive heart failure, stroke and endocrine disorders, are frequently associated with depressive symptoms. Given this, a comprehensive evaluation is mandatory. Laboratory tests are necessary to exclude concurrent metabolic, endocrine and infectious disorders, and drug effects. Imaging studies should be obtained selectively in patients with signs and symptoms, such as focal neurological findings and gait disturbances, which are suggestive of structural lesions: stroke, subdural haematoma, normal pressure hydrocephalus and brain tumours. Appropriate management involving pharmacological and nonpharmacological measures will result in significant improvement in most patients with these syndromes. Potentially offending drugs should be discontinued. In delirious patients the underlying illness must be treated concomitantly with the use of psychotropics, if necessary. Although no current medications have been shown to have a significant effect on the functional status of patients with the 2 most common causes of dementia, Alzheimer's disease and multi-infarct dementia, the management of concomitant illness in these patients may result in improved function for as long as a year. Tacrine, an anticholinesterase inhibitor, improves cognitive function slightly in selected patients with Alzheimer's disease over short periods. Finally, the treatment of depression with medications or electroconvulsive therapy (ECT) results in significant reductions in mortality and morbidity. Title: Syntheses, resolution, and structure-activity relationships of potent acetylcholinesterase inhibitors: 8-carbaphysostigmine analogues Chen YL, Nielsen J, Hedberg K, Dunaiskis A, Jones S, Russo L, Johnson J, Ives J, Liston D Ref: Journal of Medicinal Chemistry, 35:1429, 1992 : PubMed ESTHER: Chen_1992_J.Med.Chem_35_1429 PubMedSearch: Chen 1992 J.Med.Chem 35 1429 PubMedID: 1573636 Abstract The synthesis of a series of 1,2,3,3a,8,8a-hexahydroindeno[2,1-b]pyrrole 5-alkylcarbamates and their resolution are reported. These compounds are structurally related to physostigmine with substitution of a methylene group in place of the NMe group at position 8 of physostigmine. Many of these 8-carbaphysostigmine analogues are more potent acetylcholinesterase inhibitors in vitro and less toxic in vivo than physostigmine. The (-)-enantiomer (e.g., 1d and 1g) possessing the same absolute configuration at C3a and C8a as that of physostigmine, is about 6 to 12-fold more potent at inhibiting acetylcholinesterase than the corresponding (+)-enantiomer (e.g., 1e and 1h). | |||||||
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